<?xml version="1.0" encoding="us-ascii"?>
<!-- DFIN ActiveDisclosure(SM) XBRL Linkbase Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date      : 2020-02-27T17:11:18.9699153+00:00 -->
<!-- Version            : 5.0.1.321 -->
<!-- Package ID         : b6652a6e5569493b992345213d961e9a -->
<!-- Copyright (c) 2020 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" arcroleURI="http://xbrl.org/int/dim/arcrole/all" />
  <link:arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" />
  <link:arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" />
  <link:arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" />
  <link:arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" />
  <link:roleRef xlink:type="simple" xlink:href="ctmx-20191231.xsd#TemplateLink" roleURI="http://cytomx.com/20191231/role/TemplateLink" />
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/StatementBALANCESHEETS" xlink:href="ctmx-20191231.xsd#Role_StatementBALANCESHEETS" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/StatementBALANCESHEETS">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:type="locator" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockholdersEquity" xlink:type="locator" xlink:label="us-gaap_StockholdersEquity" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:type="locator" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:type="locator" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdditionalPaidInCapital" xlink:type="locator" xlink:label="us-gaap_AdditionalPaidInCapital" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockValue" xlink:type="locator" xlink:label="us-gaap_CommonStockValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PreferredStockValue" xlink:type="locator" xlink:label="us-gaap_PreferredStockValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockholdersEquityAbstract" xlink:type="locator" xlink:label="us-gaap_StockholdersEquityAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommitmentsAndContingencies" xlink:type="locator" xlink:label="us-gaap_CommitmentsAndContingencies" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Liabilities" xlink:type="locator" xlink:label="us-gaap_Liabilities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:type="locator" xlink:label="us-gaap_OtherLiabilitiesNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:type="locator" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_LiabilitiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TaxesPayableCurrent" xlink:type="locator" xlink:label="us-gaap_TaxesPayableCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_AccruedLiabilitiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:type="locator" xlink:label="us-gaap_AccountsPayableCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:type="locator" xlink:label="us-gaap_LiabilitiesCurrentAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:type="locator" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Assets" xlink:type="locator" xlink:label="us-gaap_Assets" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:type="locator" xlink:label="us-gaap_OtherAssetsNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:type="locator" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RestrictedCashNoncurrent" xlink:type="locator" xlink:label="us-gaap_RestrictedCashNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Goodwill" xlink:type="locator" xlink:label="us-gaap_Goodwill" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill" xlink:type="locator" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:type="locator" xlink:label="us-gaap_PropertyPlantAndEquipmentNet" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsCurrent" xlink:type="locator" xlink:label="us-gaap_AssetsCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent" xlink:type="locator" xlink:label="us-gaap_PrepaidExpenseAndOtherAssetsCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:type="locator" xlink:label="us-gaap_AccountsReceivableNetCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:type="locator" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsCurrentAbstract" xlink:type="locator" xlink:label="us-gaap_AssetsCurrentAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsAbstract" xlink:type="locator" xlink:label="us-gaap_AssetsAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConvertiblePreferredStockMember" xlink:type="locator" xlink:label="us-gaap_ConvertiblePreferredStockMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ClassOfStockDomain" xlink:type="locator" xlink:label="us-gaap_ClassOfStockDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ClassOfStockDomain" xlink:type="locator" xlink:label="us-gaap_ClassOfStockDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementClassOfStockAxis" xlink:type="locator" xlink:label="us-gaap_StatementClassOfStockAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementTable" xlink:type="locator" xlink:label="us-gaap_StatementTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:type="locator" xlink:label="us-gaap_StatementLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" order="10280.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementClassOfStockAxis" order="10310.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_StatementClassOfStockAxis" xlink:to="us-gaap_ClassOfStockDomain_2" order="10320.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementClassOfStockAxis" xlink:to="us-gaap_ClassOfStockDomain" order="10340.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockDomain" xlink:to="us-gaap_ConvertiblePreferredStockMember" order="10360.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AssetsAbstract" order="10390.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsAbstract" xlink:to="us-gaap_AssetsCurrentAbstract" order="10470.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue" order="10550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" order="10590.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_AccountsReceivableNetCurrent" order="10630.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_PrepaidExpenseAndOtherAssetsCurrent" order="10670.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_AssetsCurrent" order="10710.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsAbstract" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" order="10750.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsAbstract" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill" order="10790.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsAbstract" xlink:to="us-gaap_Goodwill" order="10830.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsAbstract" xlink:to="us-gaap_RestrictedCashNoncurrent" order="10870.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsAbstract" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset" order="10910.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsAbstract" xlink:to="us-gaap_OtherAssetsNoncurrent" order="10950.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsAbstract" xlink:to="us-gaap_Assets" order="10990.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract" order="11030.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract" order="11110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_AccountsPayableCurrent" order="11190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_AccruedLiabilitiesCurrent" order="11230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_TaxesPayableCurrent" order="11270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent" order="11310.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrent" order="11350.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent" order="11390.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent" order="11430.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_OtherLiabilitiesNoncurrent" order="11470.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_Liabilities" order="11510.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_CommitmentsAndContingencies" order="11550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquityAbstract" order="11590.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_PreferredStockValue" order="11670.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_CommonStockValue" order="11710.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_AdditionalPaidInCapital" order="11750.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" order="11790.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit" order="11830.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquity" order="11870.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity" order="11910.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/StatementBALANCESHEETSParenthetical" xlink:href="ctmx-20191231.xsd#Role_StatementBALANCESHEETSParenthetical" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/StatementBALANCESHEETSParenthetical">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockSharesOutstanding" xlink:type="locator" xlink:label="us-gaap_CommonStockSharesOutstanding" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockSharesIssued" xlink:type="locator" xlink:label="us-gaap_CommonStockSharesIssued" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockSharesAuthorized" xlink:type="locator" xlink:label="us-gaap_CommonStockSharesAuthorized" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare" xlink:type="locator" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PreferredStockSharesOutstanding" xlink:type="locator" xlink:label="us-gaap_PreferredStockSharesOutstanding" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PreferredStockSharesIssued" xlink:type="locator" xlink:label="us-gaap_PreferredStockSharesIssued" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PreferredStockSharesAuthorized" xlink:type="locator" xlink:label="us-gaap_PreferredStockSharesAuthorized" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PreferredStockParOrStatedValuePerShare" xlink:type="locator" xlink:label="us-gaap_PreferredStockParOrStatedValuePerShare" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConvertiblePreferredStockMember" xlink:type="locator" xlink:label="us-gaap_ConvertiblePreferredStockMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ClassOfStockDomain" xlink:type="locator" xlink:label="us-gaap_ClassOfStockDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementClassOfStockAxis" xlink:type="locator" xlink:label="us-gaap_StatementClassOfStockAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementTable" xlink:type="locator" xlink:label="us-gaap_StatementTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:type="locator" xlink:label="us-gaap_StatementLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementClassOfStockAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementClassOfStockAxis" xlink:to="us-gaap_ClassOfStockDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockDomain" xlink:to="us-gaap_ConvertiblePreferredStockMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PreferredStockParOrStatedValuePerShare" order="10180.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PreferredStockSharesAuthorized" order="10220.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PreferredStockSharesIssued" order="10260.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PreferredStockSharesOutstanding" order="10300.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare" order="10340.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockSharesAuthorized" order="10380.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockSharesIssued" order="10420.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockSharesOutstanding" order="10460.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/StatementSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:href="ctmx-20191231.xsd#Role_StatementSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/StatementSTATEMENTSOFSTOCKHOLDERSEQUITY">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLoss" xlink:type="locator" xlink:label="us-gaap_NetIncomeLoss" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" xlink:type="locator" xlink:label="us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:type="locator" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_StockIssuedDuringPeriodSharesStockPurchaseAgreement" xlink:type="locator" xlink:label="ctmx_StockIssuedDuringPeriodSharesStockPurchaseAgreement" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_StockIssuedDuringPeriodValueStockPurchaseAgreement" xlink:type="locator" xlink:label="ctmx_StockIssuedDuringPeriodValueStockPurchaseAgreement" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesIssuedForServices" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodSharesIssuedForServices" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueIssuedForServices" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodValueIssuedForServices" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CumulativeEffectOnRetainedEarningsNetOfTax1" xlink:type="locator" xlink:label="us-gaap_CumulativeEffectOnRetainedEarningsNetOfTax1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharesIssued" xlink:type="locator" xlink:label="us-gaap_SharesIssued" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockholdersEquity" xlink:type="locator" xlink:label="us-gaap_StockholdersEquity" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingStandardsUpdate201802Member" xlink:type="locator" xlink:label="us-gaap_AccountingStandardsUpdate201802Member" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingStandardsUpdate201409Member" xlink:type="locator" xlink:label="us-gaap_AccountingStandardsUpdate201409Member" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:type="locator" xlink:label="us-gaap_TypeOfAdoptionMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:type="locator" xlink:label="us-gaap_TypeOfAdoptionMember_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:type="locator" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RetainedEarningsMember" xlink:type="locator" xlink:label="us-gaap_RetainedEarningsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:type="locator" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:type="locator" xlink:label="us-gaap_AdditionalPaidInCapitalMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockMember" xlink:type="locator" xlink:label="us-gaap_CommonStockMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EquityComponentDomain" xlink:type="locator" xlink:label="us-gaap_EquityComponentDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EquityComponentDomain" xlink:type="locator" xlink:label="us-gaap_EquityComponentDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:type="locator" xlink:label="us-gaap_StatementEquityComponentsAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementTable" xlink:type="locator" xlink:label="us-gaap_StatementTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:type="locator" xlink:label="us-gaap_StatementLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementEquityComponentsAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain_2" order="10050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_CommonStockMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AdditionalPaidInCapitalMember" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_RetainedEarningsMember" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" order="10180.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember_2" order="10190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember" order="10210.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TypeOfAdoptionMember" xlink:to="us-gaap_AccountingStandardsUpdate201409Member" order="10230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TypeOfAdoptionMember" xlink:to="us-gaap_AccountingStandardsUpdate201802Member" order="10250.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockholdersEquity" order="10280.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharesIssued" order="10300.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CumulativeEffectOnRetainedEarningsNetOfTax1" order="10420.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues" order="10560.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" order="10580.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" order="10700.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" order="10720.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" order="10840.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" order="10860.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueIssuedForServices" order="10980.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesIssuedForServices" order="11000.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="ctmx_StockIssuedDuringPeriodValueStockPurchaseAgreement" order="11120.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="ctmx_StockIssuedDuringPeriodSharesStockPurchaseAgreement" order="11140.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" order="11260.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" order="11400.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" order="11540.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesScheduleOfCustomersAndCollaborationPartnersWhoRepresent10OrMoreOfTotalRevenueDuringEachPeriodPresentedOrNetAccountsReceivableBalanceDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesScheduleOfCustomersAndCollaborationPartnersWhoRepresent10OrMoreOfTotalRevenueDuringEachPeriodPresentedOrNetAccountsReceivableBalanceDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesScheduleOfCustomersAndCollaborationPartnersWhoRepresent10OrMoreOfTotalRevenueDuringEachPeriodPresentedOrNetAccountsReceivableBalanceDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:type="locator" xlink:label="us-gaap_AccountsReceivableNetCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:type="locator" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ImmunoGenIncMember" xlink:type="locator" xlink:label="ctmx_ImmunoGenIncMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_BristolMyersSquibbCompanyMember" xlink:type="locator" xlink:label="ctmx_BristolMyersSquibbCompanyMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AbbVieIrelandUnlimitedCompanyMember" xlink:type="locator" xlink:label="ctmx_AbbVieIrelandUnlimitedCompanyMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MajorCustomerMember" xlink:type="locator" xlink:label="ctmx_MajorCustomerMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:type="locator" xlink:label="srt_NameOfMajorCustomerDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:type="locator" xlink:label="srt_NameOfMajorCustomerDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MajorCustomersAxis" xlink:type="locator" xlink:label="srt_MajorCustomersAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskTable" xlink:type="locator" xlink:label="us-gaap_ConcentrationRiskTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskLineItems" xlink:type="locator" xlink:label="us-gaap_ConcentrationRiskLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ConcentrationRiskLineItems" xlink:to="us-gaap_ConcentrationRiskTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ConcentrationRiskTable" xlink:to="srt_MajorCustomersAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_MajorCustomersAxis" xlink:to="srt_NameOfMajorCustomerDomain_2" order="10050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_MajorCustomersAxis" xlink:to="srt_NameOfMajorCustomerDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_NameOfMajorCustomerDomain" xlink:to="ctmx_MajorCustomerMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ConcentrationRiskTable" xlink:to="srt_CounterpartyNameAxis" order="10160.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain_2" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AbbVieIrelandUnlimitedCompanyMember" order="10210.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_BristolMyersSquibbCompanyMember" order="10230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_ImmunoGenIncMember" order="10250.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ConcentrationRiskLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" order="10280.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ConcentrationRiskLineItems" xlink:to="us-gaap_AccountsReceivableNetCurrent" order="10700.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FinitelivedIntangibleAssetsAcquired1" xlink:type="locator" xlink:label="us-gaap_FinitelivedIntangibleAssetsAcquired1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:type="locator" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ImpairmentOfLongLivedAssetsHeldForUse" xlink:type="locator" xlink:label="us-gaap_ImpairmentOfLongLivedAssetsHeldForUse" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill" xlink:type="locator" xlink:label="us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_GoodwillImpairmentLoss" xlink:type="locator" xlink:label="us-gaap_GoodwillImpairmentLoss" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NumberOfOperatingSegments" xlink:type="locator" xlink:label="us-gaap_NumberOfOperatingSegments" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfBusinessActivities" xlink:type="locator" xlink:label="ctmx_NumberOfBusinessActivities" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ProbodyTechnologyMember" xlink:type="locator" xlink:label="ctmx_ProbodyTechnologyMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingStandardsUpdate201409Member" xlink:type="locator" xlink:label="us-gaap_AccountingStandardsUpdate201409Member" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:type="locator" xlink:label="us-gaap_TypeOfAdoptionMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:type="locator" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member" xlink:type="locator" xlink:label="us-gaap_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InitialApplicationPeriodCumulativeEffectTransitionDomain" xlink:type="locator" xlink:label="us-gaap_InitialApplicationPeriodCumulativeEffectTransitionDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InitialApplicationPeriodCumulativeEffectTransitionDomain" xlink:type="locator" xlink:label="us-gaap_InitialApplicationPeriodCumulativeEffectTransitionDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InitialApplicationPeriodCumulativeEffectTransitionAxis" xlink:type="locator" xlink:label="us-gaap_InitialApplicationPeriodCumulativeEffectTransitionAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SummaryOfSignificantAccountingPoliciesTable" xlink:type="locator" xlink:label="ctmx_SummaryOfSignificantAccountingPoliciesTable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:type="locator" xlink:label="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="ctmx_SummaryOfSignificantAccountingPoliciesTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesTable" xlink:to="us-gaap_InitialApplicationPeriodCumulativeEffectTransitionAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_InitialApplicationPeriodCumulativeEffectTransitionAxis" xlink:to="us-gaap_InitialApplicationPeriodCumulativeEffectTransitionDomain_2" order="10050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_InitialApplicationPeriodCumulativeEffectTransitionAxis" xlink:to="us-gaap_InitialApplicationPeriodCumulativeEffectTransitionDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_InitialApplicationPeriodCumulativeEffectTransitionDomain" xlink:to="us-gaap_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesTable" xlink:to="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" order="10100.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TypeOfAdoptionMember" xlink:to="us-gaap_AccountingStandardsUpdate201409Member" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" order="10160.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_2" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" order="10190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="ctmx_ProbodyTechnologyMember" order="10210.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="ctmx_NumberOfBusinessActivities" order="10260.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_NumberOfOperatingSegments" order="10280.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_GoodwillImpairmentLoss" order="10330.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill" order="10390.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ImpairmentOfLongLivedAssetsHeldForUse" order="10480.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit" order="10570.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_FinitelivedIntangibleAssetsAcquired1" order="10620.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ResearchAndDevelopmentExpense" order="10640.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesScheduleOfUsefulLivesOfPropertyAndEquipmentDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesScheduleOfUsefulLivesOfPropertyAndEquipmentDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesScheduleOfUsefulLivesOfPropertyAndEquipmentDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentEstimatedUsefulLives" xlink:type="locator" xlink:label="us-gaap_PropertyPlantAndEquipmentEstimatedUsefulLives" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife" xlink:type="locator" xlink:label="us-gaap_PropertyPlantAndEquipmentUsefulLife" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LeaseholdImprovementsMember" xlink:type="locator" xlink:label="us-gaap_LeaseholdImprovementsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FurnitureAndFixturesMember" xlink:type="locator" xlink:label="us-gaap_FurnitureAndFixturesMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ComputerEquipmentAndSoftwareMember" xlink:type="locator" xlink:label="ctmx_ComputerEquipmentAndSoftwareMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MachineryAndEquipmentMember" xlink:type="locator" xlink:label="us-gaap_MachineryAndEquipmentMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:type="locator" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:type="locator" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:type="locator" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentLineItems" xlink:type="locator" xlink:label="us-gaap_PropertyPlantAndEquipmentLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" xlink:to="us-gaap_PropertyPlantAndEquipmentByTypeAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain_2" order="10050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_MachineryAndEquipmentMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="ctmx_ComputerEquipmentAndSoftwareMember" order="10110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_FurnitureAndFixturesMember" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_LeaseholdImprovementsMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentUsefulLife" order="10180.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentEstimatedUsefulLives" order="10240.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureAdoptedAndRecentAccountingPronouncementsAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureAdoptedAndRecentAccountingPronouncementsAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureAdoptedAndRecentAccountingPronouncementsAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CumulativeEffectOnRetainedEarningsNetOfTax1" xlink:type="locator" xlink:label="us-gaap_CumulativeEffectOnRetainedEarningsNetOfTax1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:type="locator" xlink:label="us-gaap_OperatingLeaseLiability" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:type="locator" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingStandardsUpdate201802Member" xlink:type="locator" xlink:label="us-gaap_AccountingStandardsUpdate201802Member" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingStandardsUpdate201602Member" xlink:type="locator" xlink:label="us-gaap_AccountingStandardsUpdate201602Member" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:type="locator" xlink:label="us-gaap_TypeOfAdoptionMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:type="locator" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SummaryOfSignificantAccountingPoliciesTable" xlink:type="locator" xlink:label="ctmx_SummaryOfSignificantAccountingPoliciesTable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:type="locator" xlink:label="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="ctmx_SummaryOfSignificantAccountingPoliciesTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesTable" xlink:to="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TypeOfAdoptionMember" xlink:to="us-gaap_AccountingStandardsUpdate201602Member" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TypeOfAdoptionMember" xlink:to="us-gaap_AccountingStandardsUpdate201802Member" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset" order="10180.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_OperatingLeaseLiability" order="10200.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_SummaryOfSignificantAccountingPoliciesLineItems" xlink:to="us-gaap_CumulativeEffectOnRetainedEarningsNetOfTax1" order="10250.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureNetLossPerShareSummaryOfPotentiallyDilutiveSecuritiesExcludedFromComputationOfDilutedNetLossPerShareDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureNetLossPerShareSummaryOfPotentiallyDilutiveSecuritiesExcludedFromComputationOfDilutedNetLossPerShareDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureNetLossPerShareSummaryOfPotentiallyDilutiveSecuritiesExcludedFromComputationOfDilutedNetLossPerShareDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" xlink:type="locator" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockOptionMember" xlink:type="locator" xlink:label="us-gaap_StockOptionMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DerivativeContractTypeDomain" xlink:type="locator" xlink:label="us-gaap_DerivativeContractTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DerivativeContractTypeDomain" xlink:type="locator" xlink:label="us-gaap_DerivativeContractTypeDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis" xlink:type="locator" xlink:label="us-gaap_DerivativeInstrumentRiskAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:type="locator" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:to="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" xlink:to="us-gaap_DerivativeInstrumentRiskAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_DerivativeInstrumentRiskAxis" xlink:to="us-gaap_DerivativeContractTypeDomain_2" order="10050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_DerivativeInstrumentRiskAxis" xlink:to="us-gaap_DerivativeContractTypeDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DerivativeContractTypeDomain" xlink:to="us-gaap_StockOptionMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" order="10120.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureFairValueMeasurementsAndShortTermInvestmentsScheduleOfShortTermInvestmentsSubjectToFairValueMeasurementsOnRecurringBasisDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureFairValueMeasurementsAndShortTermInvestmentsScheduleOfShortTermInvestmentsSubjectToFairValueMeasurementsOnRecurringBasisDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureFairValueMeasurementsAndShortTermInvestmentsScheduleOfShortTermInvestmentsSubjectToFairValueMeasurementsOnRecurringBasisDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecurities" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleSecurities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAmortizedCost" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleSecuritiesAmortizedCost" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_USTreasuryAndGovernmentMember" xlink:type="locator" xlink:label="us-gaap_USTreasuryAndGovernmentMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MoneyMarketFundsIncludedInRestrictedCashMember" xlink:type="locator" xlink:label="ctmx_MoneyMarketFundsIncludedInRestrictedCashMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MoneyMarketFundsMember" xlink:type="locator" xlink:label="us-gaap_MoneyMarketFundsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain" xlink:type="locator" xlink:label="us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain" xlink:type="locator" xlink:label="us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueByAssetClassAxis" xlink:type="locator" xlink:label="us-gaap_FairValueByAssetClassAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueInputsLevel1Member" xlink:type="locator" xlink:label="us-gaap_FairValueInputsLevel1Member" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:type="locator" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:type="locator" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:type="locator" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:type="locator" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:type="locator" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" order="10070.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" order="10100.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_2" order="10110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel1Member" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByAssetClassAxis" order="10200.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FairValueByAssetClassAxis" xlink:to="us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_2" order="10210.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FairValueByAssetClassAxis" xlink:to="us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain" order="10230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain" xlink:to="us-gaap_MoneyMarketFundsMember" order="10250.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain" xlink:to="ctmx_MoneyMarketFundsIncludedInRestrictedCashMember" order="10270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain" xlink:to="us-gaap_USTreasuryAndGovernmentMember" order="10290.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesAmortizedCost" order="10920.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" order="11060.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" order="11200.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleSecurities" order="11340.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" order="11510.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" order="11650.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" order="11790.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities" order="11930.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureGoodwillAndIntangibleAssetsAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureGoodwillAndIntangibleAssetsAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureGoodwillAndIntangibleAssetsAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:type="locator" xlink:label="us-gaap_AmortizationOfIntangibleAssets" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife" xlink:type="locator" xlink:label="us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InProcessResearchAndDevelopmentMember" xlink:type="locator" xlink:label="us-gaap_InProcessResearchAndDevelopmentMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_InProcessResearchAndDevelopmentMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife" order="10140.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_AmortizationOfIntangibleAssets" order="10200.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureGoodwillAndIntangibleAssetsScheduleOfGoodwillAndIntangibleAssetsDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureGoodwillAndIntangibleAssetsScheduleOfGoodwillAndIntangibleAssetsDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureGoodwillAndIntangibleAssetsScheduleOfGoodwillAndIntangibleAssetsDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsGross" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsGross" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNetAbstract" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Goodwill" xlink:type="locator" xlink:label="us-gaap_Goodwill" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_GoodwillAbstract" xlink:type="locator" xlink:label="ctmx_GoodwillAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InProcessResearchAndDevelopmentMember" xlink:type="locator" xlink:label="us-gaap_InProcessResearchAndDevelopmentMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ScheduleOfGoodwillAndIntangibleAssetsTable" xlink:type="locator" xlink:label="ctmx_ScheduleOfGoodwillAndIntangibleAssetsTable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_GoodwillAndIntangibleAssetsLineItems" xlink:type="locator" xlink:label="ctmx_GoodwillAndIntangibleAssetsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="ctmx_GoodwillAndIntangibleAssetsLineItems" xlink:to="ctmx_ScheduleOfGoodwillAndIntangibleAssetsTable" order="10030.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ctmx_ScheduleOfGoodwillAndIntangibleAssetsTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" order="10060.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_InProcessResearchAndDevelopmentMember" order="10110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_GoodwillAndIntangibleAssetsLineItems" xlink:to="ctmx_GoodwillAbstract" order="10200.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_GoodwillAbstract" xlink:to="us-gaap_Goodwill" order="10280.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_GoodwillAndIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" order="10320.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsGross" order="10400.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" order="10440.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet" order="10480.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsScheduleOfRevenueByCollaborationPartnerDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsScheduleOfRevenueByCollaborationPartnerDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsScheduleOfRevenueByCollaborationPartnerDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Revenues" xlink:type="locator" xlink:label="us-gaap_Revenues" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PfizerIncMember" xlink:type="locator" xlink:label="ctmx_PfizerIncMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ImmunoGenIncMember" xlink:type="locator" xlink:label="ctmx_ImmunoGenIncMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_BristolMyersSquibbCompanyMember" xlink:type="locator" xlink:label="ctmx_BristolMyersSquibbCompanyMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AmgenIncMember" xlink:type="locator" xlink:label="ctmx_AmgenIncMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AbbVieIrelandUnlimitedCompanyMember" xlink:type="locator" xlink:label="ctmx_AbbVieIrelandUnlimitedCompanyMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AbbVieIrelandUnlimitedCompanyMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AmgenIncMember" order="10110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_BristolMyersSquibbCompanyMember" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_ImmunoGenIncMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_PfizerIncMember" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_Revenues" order="10200.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerAssetNet" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerAssetNet" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerLiability" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfRevenueExtensibleList" xlink:type="locator" xlink:label="us-gaap_TypeOfRevenueExtensibleList" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:type="locator" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EstimatedResearchServicePeriod" xlink:type="locator" xlink:label="ctmx_EstimatedResearchServicePeriod" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueRemainingPerformanceObligation" xlink:type="locator" xlink:label="us-gaap_RevenueRemainingPerformanceObligation" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_AccruedLiabilitiesCurrent" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_LicensePaymentPercentageEquivalenceToUpfrontAndMilestoneProceeds" xlink:type="locator" xlink:label="ctmx_LicensePaymentPercentageEquivalenceToUpfrontAndMilestoneProceeds" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_RevenueAdjustmentOfMilestonePaymentRecognized" xlink:type="locator" xlink:label="ctmx_RevenueAdjustmentOfMilestonePaymentRecognized" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MilestonePaymentsReceivable" xlink:type="locator" xlink:label="ctmx_MilestonePaymentsReceivable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfAccountingUnits" xlink:type="locator" xlink:label="ctmx_NumberOfAccountingUnits" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EstimatedSublicenseFees" xlink:type="locator" xlink:label="ctmx_EstimatedSublicenseFees" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AggregateCollaborationTransactionAmount" xlink:type="locator" xlink:label="ctmx_AggregateCollaborationTransactionAmount" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentMilestonePaymentsReceivable" xlink:type="locator" xlink:label="ctmx_ContingentMilestonePaymentsReceivable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MilestonePaymentReceived" xlink:type="locator" xlink:label="ctmx_MilestonePaymentReceived" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfTargetsSelected" xlink:type="locator" xlink:label="ctmx_NumberOfTargetsSelected" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfTargets" xlink:type="locator" xlink:label="ctmx_NumberOfTargets" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PaymentsOfSublicenseFees" xlink:type="locator" xlink:label="ctmx_PaymentsOfSublicenseFees" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MilestonePaymentsReceivedFromRevenueRecognizedDuringPeriod" xlink:type="locator" xlink:label="ctmx_MilestonePaymentsReceivedFromRevenueRecognizedDuringPeriod" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentPaymentsReceivableProfitSplitOnSales" xlink:type="locator" xlink:label="ctmx_ContingentPaymentsReceivableProfitSplitOnSales" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentPaymentsReceivableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" xlink:type="locator" xlink:label="ctmx_ContingentPaymentsReceivableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromCollaborators" xlink:type="locator" xlink:label="us-gaap_ProceedsFromCollaborators" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PercentageOfNetIncomeOrNetLossesRelatedToDevelopmentCosts" xlink:type="locator" xlink:label="ctmx_PercentageOfNetIncomeOrNetLossesRelatedToDevelopmentCosts" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfCollaborationAgreements" xlink:type="locator" xlink:label="ctmx_NumberOfCollaborationAgreements" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_UniversityOfCaliforniaSantaBarbaraMember" xlink:type="locator" xlink:label="ctmx_UniversityOfCaliforniaSantaBarbaraMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_RegentsOfTheUniversityOfCaliforniaMember" xlink:type="locator" xlink:label="ctmx_RegentsOfTheUniversityOfCaliforniaMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_LicenseAgreementMember" xlink:type="locator" xlink:label="ctmx_LicenseAgreementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingStandardsUpdate201409Member" xlink:type="locator" xlink:label="us-gaap_AccountingStandardsUpdate201409Member" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:type="locator" xlink:label="us-gaap_TypeOfAdoptionMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:type="locator" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SecondTargetMember" xlink:type="locator" xlink:label="ctmx_SecondTargetMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:type="locator" xlink:label="srt_ProductsAndServicesDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:type="locator" xlink:label="srt_ProductsAndServicesDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:type="locator" xlink:label="srt_ProductOrServiceAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_DevelopmentRegulatoryAndCommercialMilestonePaymentsMember" xlink:type="locator" xlink:label="ctmx_DevelopmentRegulatoryAndCommercialMilestonePaymentsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:type="locator" xlink:label="us-gaap_ContingentConsiderationTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:type="locator" xlink:label="us-gaap_ContingentConsiderationTypeDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContingentConsiderationByTypeAxis" xlink:type="locator" xlink:label="us-gaap_ContingentConsiderationByTypeAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_DiscoveryAgreementMember" xlink:type="locator" xlink:label="ctmx_DiscoveryAgreementMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SeattleGeneticsAgreementMember" xlink:type="locator" xlink:label="ctmx_SeattleGeneticsAgreementMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_CD71AgreementMember" xlink:type="locator" xlink:label="ctmx_CD71AgreementMember" />
    <link:loc xlink:href="https://xbrl.sec.gov/country/2017/country-2017-01-31.xsd#country_US" xlink:type="locator" xlink:label="country_US" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_SegmentGeographicalDomain" xlink:type="locator" xlink:label="srt_SegmentGeographicalDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_SegmentGeographicalDomain" xlink:type="locator" xlink:label="srt_SegmentGeographicalDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_StatementGeographicalAxis" xlink:type="locator" xlink:label="srt_StatementGeographicalAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MinimumMember" xlink:type="locator" xlink:label="srt_MinimumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MaximumMember" xlink:type="locator" xlink:label="srt_MaximumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:type="locator" xlink:label="srt_RangeMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:type="locator" xlink:label="srt_RangeMember_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:type="locator" xlink:label="srt_RangeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementMember" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AbbVieIrelandUnlimitedCompanyMember" xlink:type="locator" xlink:label="ctmx_AbbVieIrelandUnlimitedCompanyMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AbbVieIrelandUnlimitedCompanyMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10120.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember_2" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_RangeAxis" order="10200.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember_2" order="10210.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" order="10230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" order="10250.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" order="10270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_StatementGeographicalAxis" order="10280.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_StatementGeographicalAxis" xlink:to="srt_SegmentGeographicalDomain_2" order="10290.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_StatementGeographicalAxis" xlink:to="srt_SegmentGeographicalDomain" order="10310.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_SegmentGeographicalDomain" xlink:to="country_US" order="10330.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_CD71AgreementMember" order="10390.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_SeattleGeneticsAgreementMember" order="10490.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_DiscoveryAgreementMember" order="10770.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_ContingentConsiderationByTypeAxis" order="11080.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain_2" order="11090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain" order="11110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_DevelopmentRegulatoryAndCommercialMilestonePaymentsMember" order="11130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_ProductOrServiceAxis" order="11220.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain_2" order="11230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" order="11250.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_SecondTargetMember" order="11270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" order="11500.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember" order="11530.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TypeOfAdoptionMember" xlink:to="us-gaap_AccountingStandardsUpdate201409Member" order="11550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_LicenseAgreementMember" order="12010.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" order="12040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_2" order="12050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" order="12070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:to="ctmx_RegentsOfTheUniversityOfCaliforniaMember" order="12090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:to="ctmx_UniversityOfCaliforniaSantaBarbaraMember" order="12110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfCollaborationAgreements" order="12780.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_PercentageOfNetIncomeOrNetLossesRelatedToDevelopmentCosts" order="12800.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ProceedsFromCollaborators" order="12850.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentPaymentsReceivableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" order="12870.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentPaymentsReceivableProfitSplitOnSales" order="12890.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_MilestonePaymentsReceivedFromRevenueRecognizedDuringPeriod" order="12910.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_PaymentsOfSublicenseFees" order="12950.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfTargets" order="13040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfTargetsSelected" order="13080.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_MilestonePaymentReceived" order="13170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentMilestonePaymentsReceivable" order="13190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_AggregateCollaborationTransactionAmount" order="13240.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_EstimatedSublicenseFees" order="13320.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfAccountingUnits" order="13340.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_MilestonePaymentsReceivable" order="13400.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_RevenueAdjustmentOfMilestonePaymentRecognized" order="13550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_LicensePaymentPercentageEquivalenceToUpfrontAndMilestoneProceeds" order="13600.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_AccruedLiabilitiesCurrent" order="13640.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueRemainingPerformanceObligation" order="13770.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_EstimatedResearchServicePeriod" order="13810.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" order="13860.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_TypeOfRevenueExtensibleList" order="13920.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerLiability" order="13980.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerAssetNet" order="14100.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails1" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails1" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails1">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" xlink:type="locator" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis" xlink:type="locator" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_CD71AgreementMember" xlink:type="locator" xlink:label="ctmx_CD71AgreementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AbbVieIrelandUnlimitedCompanyMember" xlink:type="locator" xlink:label="ctmx_AbbVieIrelandUnlimitedCompanyMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AbbVieIrelandUnlimitedCompanyMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10100.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_CD71AgreementMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis" order="10160.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" order="10190.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails1Default" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails1Default" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails1Default">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" xlink:type="locator" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_CD71AgreementMember" xlink:type="locator" xlink:label="ctmx_CD71AgreementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AbbVieIrelandUnlimitedCompanyMember" xlink:type="locator" xlink:label="ctmx_AbbVieIrelandUnlimitedCompanyMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10020.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10030.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AbbVieIrelandUnlimitedCompanyMember" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10060.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_CD71AgreementMember" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" order="10080.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsAmgenIncAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsAmgenIncAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsAmgenIncAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerAssetNet" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerAssetNet" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerLiability" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfRevenueExtensibleList" xlink:type="locator" xlink:label="us-gaap_TypeOfRevenueExtensibleList" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:type="locator" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EstimatedResearchServicePeriod" xlink:type="locator" xlink:label="ctmx_EstimatedResearchServicePeriod" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueRemainingPerformanceObligation" xlink:type="locator" xlink:label="us-gaap_RevenueRemainingPerformanceObligation" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EstimatedFullTimeEmployeeHoursAndResearchServicePeriod" xlink:type="locator" xlink:label="ctmx_EstimatedFullTimeEmployeeHoursAndResearchServicePeriod" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EstimatedFairValueOfProducts" xlink:type="locator" xlink:label="ctmx_EstimatedFairValueOfProducts" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PremiumOnIssuanceOfSharesAllocatedToCommonStock" xlink:type="locator" xlink:label="ctmx_PremiumOnIssuanceOfSharesAllocatedToCommonStock" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AggregateCollaborationTransactionAmount" xlink:type="locator" xlink:label="ctmx_AggregateCollaborationTransactionAmount" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_AccruedLiabilitiesCurrent" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_LicensePaymentPercentageEquivalenceToUpfrontAndMilestoneProceeds" xlink:type="locator" xlink:label="ctmx_LicensePaymentPercentageEquivalenceToUpfrontAndMilestoneProceeds" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentPaymentsPayableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" xlink:type="locator" xlink:label="ctmx_ContingentPaymentsPayableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfAdditionalCollaborationTarget" xlink:type="locator" xlink:label="ctmx_NumberOfAdditionalCollaborationTarget" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfTargetsSelected" xlink:type="locator" xlink:label="ctmx_NumberOfTargetsSelected" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfTargets" xlink:type="locator" xlink:label="ctmx_NumberOfTargets" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ProfitShareUponExerciseOfCoDevelopmentOption" xlink:type="locator" xlink:label="ctmx_ProfitShareUponExerciseOfCoDevelopmentOption" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentMilestonePaymentsReceivable" xlink:type="locator" xlink:label="ctmx_ContingentMilestonePaymentsReceivable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EstimatedPremiumOnIssuanceOfShares" xlink:type="locator" xlink:label="ctmx_EstimatedPremiumOnIssuanceOfShares" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_LockUpPeriodForShareTransactionUnderCollaborationAndLicenseAgreement" xlink:type="locator" xlink:label="ctmx_LockUpPeriodForShareTransactionUnderCollaborationAndLicenseAgreement" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PeriodUsedToCalculateWeightedAveragePricePerShare" xlink:type="locator" xlink:label="ctmx_PeriodUsedToCalculateWeightedAveragePricePerShare" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:type="locator" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharePrice" xlink:type="locator" xlink:label="us-gaap_SharePrice" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_CommonStockSharesIssuableUnderAgreement" xlink:type="locator" xlink:label="ctmx_CommonStockSharesIssuableUnderAgreement" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromCollaborators" xlink:type="locator" xlink:label="us-gaap_ProceedsFromCollaborators" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AmgenOtherProductsMember" xlink:type="locator" xlink:label="ctmx_AmgenOtherProductsMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_RegentsOfTheUniversityOfCaliforniaMember" xlink:type="locator" xlink:label="ctmx_RegentsOfTheUniversityOfCaliforniaMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SublicenseAgreementMember" xlink:type="locator" xlink:label="ctmx_SublicenseAgreementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MinimumMember" xlink:type="locator" xlink:label="srt_MinimumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MaximumMember" xlink:type="locator" xlink:label="srt_MaximumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:type="locator" xlink:label="srt_RangeMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:type="locator" xlink:label="srt_RangeAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EGFRProductsMember" xlink:type="locator" xlink:label="ctmx_EGFRProductsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:type="locator" xlink:label="srt_ProductsAndServicesDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:type="locator" xlink:label="srt_ProductOrServiceAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AmgenIncMember" xlink:type="locator" xlink:label="ctmx_AmgenIncMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_CollaborationAndLicenseAgreementMember" xlink:type="locator" xlink:label="ctmx_CollaborationAndLicenseAgreementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_CollaborationAndLicenseAgreementMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10220.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10250.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AmgenIncMember" order="10270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_ProductOrServiceAxis" order="10560.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" order="10590.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_EGFRProductsMember" order="10610.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_RangeAxis" order="10640.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" order="10670.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" order="10690.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" order="10730.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_SublicenseAgreementMember" order="11330.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" order="11440.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" order="11470.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:to="ctmx_RegentsOfTheUniversityOfCaliforniaMember" order="11490.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_AmgenOtherProductsMember" order="12110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ProceedsFromCollaborators" order="12740.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_CommonStockSharesIssuableUnderAgreement" order="12760.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_SharePrice" order="12780.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock" order="12800.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_PeriodUsedToCalculateWeightedAveragePricePerShare" order="12820.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_LockUpPeriodForShareTransactionUnderCollaborationAndLicenseAgreement" order="12840.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_EstimatedPremiumOnIssuanceOfShares" order="12860.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentMilestonePaymentsReceivable" order="12910.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ProfitShareUponExerciseOfCoDevelopmentOption" order="12930.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfTargets" order="12980.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfTargetsSelected" order="13000.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfAdditionalCollaborationTarget" order="13020.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentPaymentsPayableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" order="13090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_LicensePaymentPercentageEquivalenceToUpfrontAndMilestoneProceeds" order="13140.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_AccruedLiabilitiesCurrent" order="13160.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_AggregateCollaborationTransactionAmount" order="13230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_PremiumOnIssuanceOfSharesAllocatedToCommonStock" order="13270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_EstimatedFairValueOfProducts" order="13290.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_EstimatedFullTimeEmployeeHoursAndResearchServicePeriod" order="13400.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueRemainingPerformanceObligation" order="13470.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_EstimatedResearchServicePeriod" order="13490.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" order="13540.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_TypeOfRevenueExtensibleList" order="13600.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerLiability" order="13660.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerAssetNet" order="13780.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsBristolMyersSquibbCompanyAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsBristolMyersSquibbCompanyAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsBristolMyersSquibbCompanyAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerAssetNet" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerAssetNet" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerLiability" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfRevenueExtensibleList" xlink:type="locator" xlink:label="us-gaap_TypeOfRevenueExtensibleList" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:type="locator" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EstimatedResearchServiceTerminationDate" xlink:type="locator" xlink:label="ctmx_EstimatedResearchServiceTerminationDate" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MilestonePaymentsReceivedFromRevenueRecognizedDuringPeriod" xlink:type="locator" xlink:label="ctmx_MilestonePaymentsReceivedFromRevenueRecognizedDuringPeriod" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ResearchAndDevelopmentServiceFees" xlink:type="locator" xlink:label="ctmx_ResearchAndDevelopmentServiceFees" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueRemainingPerformanceObligation" xlink:type="locator" xlink:label="us-gaap_RevenueRemainingPerformanceObligation" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfNonOncologyTarget" xlink:type="locator" xlink:label="ctmx_NumberOfNonOncologyTarget" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfSalesIndicatorsForEachResearchTargetProgram" xlink:type="locator" xlink:label="ctmx_NumberOfSalesIndicatorsForEachResearchTargetProgram" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfResearchTargetsSelected" xlink:type="locator" xlink:label="ctmx_NumberOfResearchTargetsSelected" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentMilestonePaymentsReceivable" xlink:type="locator" xlink:label="ctmx_ContingentMilestonePaymentsReceivable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromCollaborators" xlink:type="locator" xlink:label="us-gaap_ProceedsFromCollaborators" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_IncrementsOfExtendedCollaborationTargetResearchTimes" xlink:type="locator" xlink:label="ctmx_IncrementsOfExtendedCollaborationTargetResearchTimes" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ExtensionOfResearchTermForEachCollaborationTarget" xlink:type="locator" xlink:label="ctmx_ExtensionOfResearchTermForEachCollaborationTarget" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PeriodOfNominationOfAdditionalTarget" xlink:type="locator" xlink:label="ctmx_PeriodOfNominationOfAdditionalTarget" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersDescriptionAndTerms" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersDescriptionAndTerms" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfAdditionalCollaborationTarget" xlink:type="locator" xlink:label="ctmx_NumberOfAdditionalCollaborationTarget" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_CollaborationTargetResearchTerm" xlink:type="locator" xlink:label="ctmx_CollaborationTargetResearchTerm" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfCollaborationTarget" xlink:type="locator" xlink:label="ctmx_NumberOfCollaborationTarget" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfOncologyTarget" xlink:type="locator" xlink:label="ctmx_NumberOfOncologyTarget" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ThirdAndFourthTargetsMember" xlink:type="locator" xlink:label="ctmx_ThirdAndFourthTargetsMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingSalesMilestonePaymentIfEightResearchTargetAreSelectedForSecondProductModalityMember" xlink:type="locator" xlink:label="ctmx_AchievingSalesMilestonePaymentIfEightResearchTargetAreSelectedForSecondProductModalityMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingSalesMilestonePaymentsPerTargetMember" xlink:type="locator" xlink:label="ctmx_AchievingSalesMilestonePaymentsPerTargetMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingMilestonePaymentIfEightResearchTargetAreSelectedForSecondProductModalityMember" xlink:type="locator" xlink:label="ctmx_AchievingMilestonePaymentIfEightResearchTargetAreSelectedForSecondProductModalityMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingMilestonePaymentsForFirstCommercialSaleInVariousTerritoriesForUpToThreeIndicationsMember" xlink:type="locator" xlink:label="ctmx_AchievingMilestonePaymentsForFirstCommercialSaleInVariousTerritoriesForUpToThreeIndicationsMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingDevelopmentMilestonePaymentIfEightResearchTargetsAreSelectedForSecondProductModalityMember" xlink:type="locator" xlink:label="ctmx_AchievingDevelopmentMilestonePaymentIfEightResearchTargetsAreSelectedForSecondProductModalityMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingDevelopmentMilestonePaymentsMember" xlink:type="locator" xlink:label="ctmx_AchievingDevelopmentMilestonePaymentsMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingSalesMilestonesIfEightResearchTargetsSelectedForFirstProductModalityMember" xlink:type="locator" xlink:label="ctmx_AchievingSalesMilestonesIfEightResearchTargetsSelectedForFirstProductModalityMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingEightTargetsSelectedForFirstProductModalityMember" xlink:type="locator" xlink:label="ctmx_AchievingEightTargetsSelectedForFirstProductModalityMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievementOfDevelopmentMilestonesIfEightResearchTargetsSelectedByCounterpartyMember" xlink:type="locator" xlink:label="ctmx_AchievementOfDevelopmentMilestonesIfEightResearchTargetsSelectedByCounterpartyMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_CollaborationAndLicenseAgreementMember" xlink:type="locator" xlink:label="ctmx_CollaborationAndLicenseAgreementMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_DrugApplicationForCTLA4Member" xlink:type="locator" xlink:label="ctmx_DrugApplicationForCTLA4Member" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PreClinicalCandidateMember" xlink:type="locator" xlink:label="ctmx_PreClinicalCandidateMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:type="locator" xlink:label="srt_ProductsAndServicesDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:type="locator" xlink:label="srt_ProductOrServiceAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingSalesMilestonesIfFourResearchTargetsSelectedByCounterpartyMember" xlink:type="locator" xlink:label="ctmx_AchievingSalesMilestonesIfFourResearchTargetsSelectedByCounterpartyMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingSalesMilestonesForEachResearchTargetProgramMember" xlink:type="locator" xlink:label="ctmx_AchievingSalesMilestonesForEachResearchTargetProgramMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingFirstCommercialSaleIfFourResearchTargetsSelectedByCounterpartyMember" xlink:type="locator" xlink:label="ctmx_AchievingFirstCommercialSaleIfFourResearchTargetsSelectedByCounterpartyMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingFirstCommercialSaleInVariousTerritoriesMember" xlink:type="locator" xlink:label="ctmx_AchievingFirstCommercialSaleInVariousTerritoriesMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievementOfDevelopmentMilestonesIfFourResearchTargetsSelectedByCounterpartyMember" xlink:type="locator" xlink:label="ctmx_AchievementOfDevelopmentMilestonesIfFourResearchTargetsSelectedByCounterpartyMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievementOfDevelopmentMilestonesForEachResearchTargetProgramMember" xlink:type="locator" xlink:label="ctmx_AchievementOfDevelopmentMilestonesForEachResearchTargetProgramMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AchievingAdditionalTargetsMember" xlink:type="locator" xlink:label="ctmx_AchievingAdditionalTargetsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:type="locator" xlink:label="us-gaap_ContingentConsiderationTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContingentConsiderationByTypeAxis" xlink:type="locator" xlink:label="us-gaap_ContingentConsiderationByTypeAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_BristolMyersSquibbCompanyMember" xlink:type="locator" xlink:label="ctmx_BristolMyersSquibbCompanyMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MinimumMember" xlink:type="locator" xlink:label="srt_MinimumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MaximumMember" xlink:type="locator" xlink:label="srt_MaximumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:type="locator" xlink:label="srt_RangeMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:type="locator" xlink:label="srt_RangeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementMember" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_RangeAxis" order="10240.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" order="10270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" order="10290.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" order="10370.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10380.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10410.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_BristolMyersSquibbCompanyMember" order="10430.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_ContingentConsiderationByTypeAxis" order="11480.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain" order="11510.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingAdditionalTargetsMember" order="11530.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievementOfDevelopmentMilestonesForEachResearchTargetProgramMember" order="11550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievementOfDevelopmentMilestonesIfFourResearchTargetsSelectedByCounterpartyMember" order="11570.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingFirstCommercialSaleInVariousTerritoriesMember" order="11610.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingFirstCommercialSaleIfFourResearchTargetsSelectedByCounterpartyMember" order="11650.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingSalesMilestonesForEachResearchTargetProgramMember" order="11690.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingSalesMilestonesIfFourResearchTargetsSelectedByCounterpartyMember" order="11710.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_ProductOrServiceAxis" order="11860.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" order="11890.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_PreClinicalCandidateMember" order="11910.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_DrugApplicationForCTLA4Member" order="11930.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_CollaborationAndLicenseAgreementMember" order="11990.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievementOfDevelopmentMilestonesIfEightResearchTargetsSelectedByCounterpartyMember" order="12810.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingEightTargetsSelectedForFirstProductModalityMember" order="12890.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingSalesMilestonesIfEightResearchTargetsSelectedForFirstProductModalityMember" order="12950.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingDevelopmentMilestonePaymentsMember" order="12990.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingDevelopmentMilestonePaymentIfEightResearchTargetsAreSelectedForSecondProductModalityMember" order="13010.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingMilestonePaymentsForFirstCommercialSaleInVariousTerritoriesForUpToThreeIndicationsMember" order="13050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingMilestonePaymentIfEightResearchTargetAreSelectedForSecondProductModalityMember" order="13090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingSalesMilestonePaymentsPerTargetMember" order="13130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="ctmx_AchievingSalesMilestonePaymentIfEightResearchTargetAreSelectedForSecondProductModalityMember" order="13150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_ThirdAndFourthTargetsMember" order="13630.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfOncologyTarget" order="13660.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfCollaborationTarget" order="13680.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_CollaborationTargetResearchTerm" order="13700.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfAdditionalCollaborationTarget" order="13720.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersDescriptionAndTerms" order="13740.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_PeriodOfNominationOfAdditionalTarget" order="13760.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ExtensionOfResearchTermForEachCollaborationTarget" order="13780.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_IncrementsOfExtendedCollaborationTargetResearchTimes" order="13800.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ProceedsFromCollaborators" order="13850.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentMilestonePaymentsReceivable" order="13870.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfResearchTargetsSelected" order="13950.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfSalesIndicatorsForEachResearchTargetProgram" order="13990.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfNonOncologyTarget" order="14310.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueRemainingPerformanceObligation" order="14830.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ResearchAndDevelopmentServiceFees" order="14870.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_MilestonePaymentsReceivedFromRevenueRecognizedDuringPeriod" order="14890.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_EstimatedResearchServiceTerminationDate" order="14910.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" order="14960.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_TypeOfRevenueExtensibleList" order="15080.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerLiability" order="15140.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerAssetNet" order="15200.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsImmunogenIncAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsImmunogenIncAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsImmunogenIncAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerAssetNet" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerAssetNet" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfRevenueExtensibleList" xlink:type="locator" xlink:label="us-gaap_TypeOfRevenueExtensibleList" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:type="locator" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EstimatedFairValueOfAssetsAndServices" xlink:type="locator" xlink:label="ctmx_EstimatedFairValueOfAssetsAndServices" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerLiability" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MilestonePaymentPayable" xlink:type="locator" xlink:label="ctmx_MilestonePaymentPayable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MilestonesPaymentsMadeDuringPeriod" xlink:type="locator" xlink:label="ctmx_MilestonesPaymentsMadeDuringPeriod" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentPaymentsPayableUponAchievingSalesMilestones" xlink:type="locator" xlink:label="ctmx_ContingentPaymentsPayableUponAchievingSalesMilestones" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentPaymentsPayableUponAchievingDevelopmentAndRegulatoryMilestones" xlink:type="locator" xlink:label="ctmx_ContingentPaymentsPayableUponAchievingDevelopmentAndRegulatoryMilestones" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentPaymentsReceivableUponAchievingSalesMilestones" xlink:type="locator" xlink:label="ctmx_ContingentPaymentsReceivableUponAchievingSalesMilestones" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentPaymentsReceivableUponAchievingDevelopmentAndRegulatoryMilestones" xlink:type="locator" xlink:label="ctmx_ContingentPaymentsReceivableUponAchievingDevelopmentAndRegulatoryMilestones" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfResearchTargetsSelected" xlink:type="locator" xlink:label="ctmx_NumberOfResearchTargetsSelected" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_CashPaymentToExecuteAgreement" xlink:type="locator" xlink:label="ctmx_CashPaymentToExecuteAgreement" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ResearchServicesJointResearchCommitteeParticipationAndTechnologyImprovementsMember" xlink:type="locator" xlink:label="ctmx_ResearchServicesJointResearchCommitteeParticipationAndTechnologyImprovementsMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_LicenseReceivablesMember" xlink:type="locator" xlink:label="ctmx_LicenseReceivablesMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TransactionDomain" xlink:type="locator" xlink:label="us-gaap_TransactionDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TransactionDomain" xlink:type="locator" xlink:label="us-gaap_TransactionDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TransactionTypeAxis" xlink:type="locator" xlink:label="us-gaap_TransactionTypeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LicenseAgreementTermsMember" xlink:type="locator" xlink:label="us-gaap_LicenseAgreementTermsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MinimumMember" xlink:type="locator" xlink:label="srt_MinimumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MaximumMember" xlink:type="locator" xlink:label="srt_MaximumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:type="locator" xlink:label="srt_RangeMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:type="locator" xlink:label="srt_RangeAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ImmunoGenIncMember" xlink:type="locator" xlink:label="ctmx_ImmunoGenIncMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementMember" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10120.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_ImmunoGenIncMember" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_RangeAxis" order="10520.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" order="10550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" order="10570.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" order="10650.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" order="10660.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" order="10690.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:to="us-gaap_LicenseAgreementTermsMember" order="10710.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TransactionTypeAxis" order="11060.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_TransactionTypeAxis" xlink:to="us-gaap_TransactionDomain_2" order="11070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TransactionTypeAxis" xlink:to="us-gaap_TransactionDomain" order="11090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TransactionDomain" xlink:to="ctmx_LicenseReceivablesMember" order="11110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TransactionDomain" xlink:to="ctmx_ResearchServicesJointResearchCommitteeParticipationAndTechnologyImprovementsMember" order="11130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_CashPaymentToExecuteAgreement" order="11400.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfResearchTargetsSelected" order="11440.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentPaymentsReceivableUponAchievingDevelopmentAndRegulatoryMilestones" order="11510.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentPaymentsReceivableUponAchievingSalesMilestones" order="11550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentPaymentsPayableUponAchievingDevelopmentAndRegulatoryMilestones" order="11590.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContingentPaymentsPayableUponAchievingSalesMilestones" order="11630.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_MilestonesPaymentsMadeDuringPeriod" order="11670.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_MilestonePaymentPayable" order="11710.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerLiability" order="11780.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_EstimatedFairValueOfAssetsAndServices" order="11830.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" order="11920.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_TypeOfRevenueExtensibleList" order="11980.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerAssetNet" order="12100.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsMDAndersonAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsMDAndersonAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsMDAndersonAdditionalInformationDetails">
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_OptionsExpirationDate" xlink:type="locator" xlink:label="ctmx_OptionsExpirationDate" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MDAndersonMember" xlink:type="locator" xlink:label="ctmx_MDAndersonMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementMember" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10100.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_MDAndersonMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_OptionsExpirationDate" order="10180.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsPfizerIncAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsPfizerIncAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsPfizerIncAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerAssetNet" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerAssetNet" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerLiability" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfRevenueExtensibleList" xlink:type="locator" xlink:label="us-gaap_TypeOfRevenueExtensibleList" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:type="locator" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AmortizationPeriodOfDeferredRevenue" xlink:type="locator" xlink:label="ctmx_AmortizationPeriodOfDeferredRevenue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromCollaborators" xlink:type="locator" xlink:label="us-gaap_ProceedsFromCollaborators" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContractWithCustomerLiabilityAdditions" xlink:type="locator" xlink:label="ctmx_ContractWithCustomerLiabilityAdditions" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfAdditionalResearchTargetsWithNominationOption" xlink:type="locator" xlink:label="ctmx_NumberOfAdditionalResearchTargetsWithNominationOption" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NumberOfNominatedResearchTargets" xlink:type="locator" xlink:label="ctmx_NumberOfNominatedResearchTargets" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PfizerIncMember" xlink:type="locator" xlink:label="ctmx_PfizerIncMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementMember" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10140.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_PfizerIncMember" order="10190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfNominatedResearchTargets" order="10740.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_NumberOfAdditionalResearchTargetsWithNominationOption" order="10760.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContractWithCustomerLiabilityAdditions" order="10780.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ProceedsFromCollaborators" order="10830.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_AmortizationPeriodOfDeferredRevenue" order="10880.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" order="10930.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_TypeOfRevenueExtensibleList" order="10990.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerLiability" order="11050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerAssetNet" order="11110.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsContractLiabilitiesAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureResearchAndCollaborationAgreementsContractLiabilitiesAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureResearchAndCollaborationAgreementsContractLiabilitiesAdditionalInformationDetails">
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContractWithCustomerLiabilityMaturityMonthAndYear" xlink:type="locator" xlink:label="ctmx_ContractWithCustomerLiabilityMaturityMonthAndYear" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerLiability" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:type="locator" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:type="locator" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContractWithCustomerLiabilityAdditions" xlink:type="locator" xlink:label="ctmx_ContractWithCustomerLiabilityAdditions" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AmgenOtherProductsMember" xlink:type="locator" xlink:label="ctmx_AmgenOtherProductsMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EGFRProductsMember" xlink:type="locator" xlink:label="ctmx_EGFRProductsMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_FirstTargetMember" xlink:type="locator" xlink:label="ctmx_FirstTargetMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_DiscoveryAgreementMember" xlink:type="locator" xlink:label="ctmx_DiscoveryAgreementMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_CD71AgreementMember" xlink:type="locator" xlink:label="ctmx_CD71AgreementMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AmgenIncMember" xlink:type="locator" xlink:label="ctmx_AmgenIncMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ThirdAndFourthTargetsMember" xlink:type="locator" xlink:label="ctmx_ThirdAndFourthTargetsMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SecondTargetMember" xlink:type="locator" xlink:label="ctmx_SecondTargetMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:type="locator" xlink:label="srt_ProductsAndServicesDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:type="locator" xlink:label="srt_ProductOrServiceAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_BristolMyersSquibbCompanyMember" xlink:type="locator" xlink:label="ctmx_BristolMyersSquibbCompanyMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AbbVieIrelandUnlimitedCompanyMember" xlink:type="locator" xlink:label="ctmx_AbbVieIrelandUnlimitedCompanyMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementMember" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" order="10100.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AbbVieIrelandUnlimitedCompanyMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_BristolMyersSquibbCompanyMember" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_ProductOrServiceAxis" order="10180.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" order="10210.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_SecondTargetMember" order="10230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_ThirdAndFourthTargetsMember" order="10250.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AmgenIncMember" order="10370.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_CD71AgreementMember" order="10470.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_DiscoveryAgreementMember" order="10490.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_FirstTargetMember" order="10570.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_EGFRProductsMember" order="10610.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_AmgenOtherProductsMember" order="10630.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContractWithCustomerLiabilityAdditions" order="10660.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized" order="10680.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" order="10700.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerLiability" order="10750.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ctmx_ContractWithCustomerLiabilityMaturityMonthAndYear" order="10890.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureLicenseAgreementAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureLicenseAgreementAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureLicenseAgreementAdditionalInformationDetails">
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_UpfrontLicensePayment" xlink:type="locator" xlink:label="ctmx_UpfrontLicensePayment" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_AccruedLiabilitiesCurrent" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SublicenseFees" xlink:type="locator" xlink:label="ctmx_SublicenseFees" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MilestonePaymentReceivable" xlink:type="locator" xlink:label="ctmx_MilestonePaymentReceivable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AdditionalSublicenseFees" xlink:type="locator" xlink:label="ctmx_AdditionalSublicenseFees" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_FairValueOfCommonStockIssued" xlink:type="locator" xlink:label="ctmx_FairValueOfCommonStockIssued" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentExpense" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PercentageOfRemainingMaintenanceFeesOutstanding" xlink:type="locator" xlink:label="ctmx_PercentageOfRemainingMaintenanceFeesOutstanding" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_LicensePaymentTerm" xlink:type="locator" xlink:label="ctmx_LicensePaymentTerm" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AnnualLicenseMaintenanceFees" xlink:type="locator" xlink:label="ctmx_AnnualLicenseMaintenanceFees" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PaymentOfUpfrontFees" xlink:type="locator" xlink:label="ctmx_PaymentOfUpfrontFees" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharesIssuedPricePerShare" xlink:type="locator" xlink:label="us-gaap_SharesIssuedPricePerShare" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockSharesIssued" xlink:type="locator" xlink:label="us-gaap_CommonStockSharesIssued" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_LicenseTerminationPeriod" xlink:type="locator" xlink:label="ctmx_LicenseTerminationPeriod" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_RoyaltyObligationsFutureMinimumPaymentsDue" xlink:type="locator" xlink:label="ctmx_RoyaltyObligationsFutureMinimumPaymentsDue" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ImmunoGenIncMember" xlink:type="locator" xlink:label="ctmx_ImmunoGenIncMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementMember" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SecondTargetMember" xlink:type="locator" xlink:label="ctmx_SecondTargetMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:type="locator" xlink:label="srt_ProductsAndServicesDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:type="locator" xlink:label="srt_ProductOrServiceAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_DiscoveryAgreementMember" xlink:type="locator" xlink:label="ctmx_DiscoveryAgreementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_AbbVieMember" xlink:type="locator" xlink:label="ctmx_AbbVieMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SublicenseAndMaintenanceFeesMember" xlink:type="locator" xlink:label="ctmx_SublicenseAndMaintenanceFeesMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:type="locator" xlink:label="us-gaap_IncomeStatementLocationDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:type="locator" xlink:label="us-gaap_IncomeStatementLocationDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:type="locator" xlink:label="us-gaap_IncomeStatementLocationAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_UniversityOfCaliforniaSantaBarbaraMember" xlink:type="locator" xlink:label="ctmx_UniversityOfCaliforniaSantaBarbaraMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:to="ctmx_UniversityOfCaliforniaSantaBarbaraMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:to="us-gaap_IncomeStatementLocationAxis" order="10100.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain_2" order="10110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="ctmx_SublicenseAndMaintenanceFeesMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:to="srt_CounterpartyNameAxis" order="10220.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10250.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_AbbVieMember" order="10270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10300.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10330.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="ctmx_DiscoveryAgreementMember" order="10350.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:to="srt_ProductOrServiceAxis" order="10380.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" order="10410.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="ctmx_SecondTargetMember" order="10430.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" order="10590.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_ImmunoGenIncMember" order="10650.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_RoyaltyObligationsFutureMinimumPaymentsDue" order="10800.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_LicenseTerminationPeriod" order="10820.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="us-gaap_CommonStockSharesIssued" order="10870.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="us-gaap_SharesIssuedPricePerShare" order="10940.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_PaymentOfUpfrontFees" order="10960.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_AnnualLicenseMaintenanceFees" order="10980.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_LicensePaymentTerm" order="11000.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_PercentageOfRemainingMaintenanceFeesOutstanding" order="11020.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="us-gaap_ResearchAndDevelopmentExpense" order="11040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_FairValueOfCommonStockIssued" order="11080.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_AdditionalSublicenseFees" order="11170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_MilestonePaymentReceivable" order="11190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_SublicenseFees" order="11240.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="us-gaap_AccruedLiabilitiesCurrent" order="11300.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems" xlink:to="ctmx_UpfrontLicensePayment" order="11390.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureLeasesAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureLeasesAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureLeasesAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseExpense" xlink:type="locator" xlink:label="us-gaap_OperatingLeaseExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RestrictedCashNoncurrent" xlink:type="locator" xlink:label="us-gaap_RestrictedCashNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LettersOfCreditOutstandingAmount" xlink:type="locator" xlink:label="us-gaap_LettersOfCreditOutstandingAmount" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ImprovementAllowanceFromRecoverableRent" xlink:type="locator" xlink:label="ctmx_ImprovementAllowanceFromRecoverableRent" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MaximumImprovementAllowance" xlink:type="locator" xlink:label="ctmx_MaximumImprovementAllowance" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_OperatingLeasesRentExpenseAnnualBaseRent" xlink:type="locator" xlink:label="ctmx_OperatingLeasesRentExpenseAnnualBaseRent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm" xlink:type="locator" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:type="locator" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseDescription" xlink:type="locator" xlink:label="us-gaap_LesseeOperatingLeaseDescription" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AreaOfLand" xlink:type="locator" xlink:label="us-gaap_AreaOfLand" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LetterOfCreditMember" xlink:type="locator" xlink:label="us-gaap_LetterOfCreditMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CreditFacilityDomain" xlink:type="locator" xlink:label="us-gaap_CreditFacilityDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CreditFacilityDomain" xlink:type="locator" xlink:label="us-gaap_CreditFacilityDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CreditFacilityAxis" xlink:type="locator" xlink:label="us-gaap_CreditFacilityAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_TenthYearOfLeaseTermMember" xlink:type="locator" xlink:label="ctmx_TenthYearOfLeaseTermMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_SecondTwelveMonthsOfLeaseTermMember" xlink:type="locator" xlink:label="ctmx_SecondTwelveMonthsOfLeaseTermMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_FirstYearOfLeaseTermMember" xlink:type="locator" xlink:label="ctmx_FirstYearOfLeaseTermMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LeaseArrangementTypeDomain" xlink:type="locator" xlink:label="us-gaap_LeaseArrangementTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LeaseArrangementTypeDomain" xlink:type="locator" xlink:label="us-gaap_LeaseArrangementTypeDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LeaseArrangementTypeAxis" xlink:type="locator" xlink:label="us-gaap_LeaseArrangementTypeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LeaseAgreementsMember" xlink:type="locator" xlink:label="us-gaap_LeaseAgreementsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="locator" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfOperatingLeasedAssetsTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfOperatingLeasedAssetsTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeasedAssetsLineItems" xlink:type="locator" xlink:label="us-gaap_OperatingLeasedAssetsLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="us-gaap_ScheduleOfOperatingLeasedAssetsTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfOperatingLeasedAssetsTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_LeaseAgreementsMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfOperatingLeasedAssetsTable" xlink:to="us-gaap_LeaseArrangementTypeAxis" order="10220.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_LeaseArrangementTypeAxis" xlink:to="us-gaap_LeaseArrangementTypeDomain_2" order="10230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_LeaseArrangementTypeAxis" xlink:to="us-gaap_LeaseArrangementTypeDomain" order="10250.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LeaseArrangementTypeDomain" xlink:to="ctmx_FirstYearOfLeaseTermMember" order="10270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LeaseArrangementTypeDomain" xlink:to="ctmx_SecondTwelveMonthsOfLeaseTermMember" order="10290.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LeaseArrangementTypeDomain" xlink:to="ctmx_TenthYearOfLeaseTermMember" order="10310.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfOperatingLeasedAssetsTable" xlink:to="us-gaap_CreditFacilityAxis" order="10320.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_CreditFacilityAxis" xlink:to="us-gaap_CreditFacilityDomain_2" order="10330.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_CreditFacilityAxis" xlink:to="us-gaap_CreditFacilityDomain" order="10350.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CreditFacilityDomain" xlink:to="us-gaap_LetterOfCreditMember" order="10370.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="us-gaap_AreaOfLand" order="10420.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="us-gaap_LesseeOperatingLeaseDescription" order="10470.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="us-gaap_LesseeOperatingLeaseTermOfContract" order="10490.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm" order="10510.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="ctmx_OperatingLeasesRentExpenseAnnualBaseRent" order="10560.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="ctmx_MaximumImprovementAllowance" order="10620.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="ctmx_ImprovementAllowanceFromRecoverableRent" order="10640.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="us-gaap_LettersOfCreditOutstandingAmount" order="10690.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="us-gaap_RestrictedCashNoncurrent" order="10730.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLeasedAssetsLineItems" xlink:to="us-gaap_OperatingLeaseExpense" order="10800.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureCommonStockAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureCommonStockAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureCommonStockAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PaymentsOfStockIssuanceCosts" xlink:type="locator" xlink:label="us-gaap_PaymentsOfStockIssuanceCosts" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:type="locator" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharesIssuedPricePerShare" xlink:type="locator" xlink:label="us-gaap_SharesIssuedPricePerShare" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DividendsCommonStock" xlink:type="locator" xlink:label="us-gaap_DividendsCommonStock" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PreferredStockParOrStatedValuePerShare" xlink:type="locator" xlink:label="us-gaap_PreferredStockParOrStatedValuePerShare" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PreferredStockSharesAuthorized" xlink:type="locator" xlink:label="us-gaap_PreferredStockSharesAuthorized" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare" xlink:type="locator" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockSharesAuthorized" xlink:type="locator" xlink:label="us-gaap_CommonStockSharesAuthorized" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OverAllotmentOptionMember" xlink:type="locator" xlink:label="us-gaap_OverAllotmentOptionMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_UnderwrittenPublicOfferingMember" xlink:type="locator" xlink:label="ctmx_UnderwrittenPublicOfferingMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:type="locator" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:type="locator" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:type="locator" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockMember" xlink:type="locator" xlink:label="us-gaap_CommonStockMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EquityComponentDomain" xlink:type="locator" xlink:label="us-gaap_EquityComponentDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:type="locator" xlink:label="us-gaap_StatementEquityComponentsAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfStockByClassTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfStockByClassTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ClassOfStockLineItems" xlink:type="locator" xlink:label="us-gaap_ClassOfStockLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_ScheduleOfStockByClassTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfStockByClassTable" xlink:to="us-gaap_StatementEquityComponentsAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_CommonStockMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfStockByClassTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" order="10180.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain_2" order="10190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" order="10210.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="ctmx_UnderwrittenPublicOfferingMember" order="10230.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="us-gaap_OverAllotmentOptionMember" order="10270.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_CommonStockSharesAuthorized" order="10300.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare" order="10360.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_PreferredStockSharesAuthorized" order="10420.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_PreferredStockParOrStatedValuePerShare" order="10480.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_DividendsCommonStock" order="10540.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" order="10630.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_SharesIssuedPricePerShare" order="10650.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock" order="10690.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_PaymentsOfStockIssuanceCosts" order="10710.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureStockBasedCompensationAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureStockBasedCompensationAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureStockBasedCompensationAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:type="locator" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:type="locator" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:type="locator" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:type="locator" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:type="locator" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:type="locator" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardVotingRightsOfCommonStockHoldingPercentage" xlink:type="locator" xlink:label="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardVotingRightsOfCommonStockHoldingPercentage" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:type="locator" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfOutstandingStockMaximum" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfOutstandingStockMaximum" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" xlink:type="locator" xlink:label="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_NonEmployeesMember" xlink:type="locator" xlink:label="ctmx_NonEmployeesMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EmployeeStockPurchasePlanMember" xlink:type="locator" xlink:label="ctmx_EmployeeStockPurchasePlanMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EarlyExerciseOfEmployeeOptionsMember" xlink:type="locator" xlink:label="ctmx_EarlyExerciseOfEmployeeOptionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:type="locator" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AwardTypeAxis" xlink:type="locator" xlink:label="us-gaap_AwardTypeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheTwoMember" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheTwoMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheOneMember" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheOneMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_VestingDomain" xlink:type="locator" xlink:label="us-gaap_VestingDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_VestingDomain" xlink:type="locator" xlink:label="us-gaap_VestingDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_VestingAxis" xlink:type="locator" xlink:label="us-gaap_VestingAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_TwoThousandNineteenStockIncentivePlanMember" xlink:type="locator" xlink:label="ctmx_TwoThousandNineteenStockIncentivePlanMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_TwoThousandFifteenStockIncentivePlanMember" xlink:type="locator" xlink:label="ctmx_TwoThousandFifteenStockIncentivePlanMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameDomain" xlink:type="locator" xlink:label="us-gaap_PlanNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameDomain" xlink:type="locator" xlink:label="us-gaap_PlanNameDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameAxis" xlink:type="locator" xlink:label="us-gaap_PlanNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MaximumMember" xlink:type="locator" xlink:label="srt_MaximumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MinimumMember" xlink:type="locator" xlink:label="srt_MinimumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:type="locator" xlink:label="srt_RangeMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:type="locator" xlink:label="srt_RangeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="srt_RangeAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" order="10110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_PlanNameAxis" order="10160.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain_2" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain" order="10190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PlanNameDomain" xlink:to="ctmx_TwoThousandFifteenStockIncentivePlanMember" order="10210.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PlanNameDomain" xlink:to="ctmx_TwoThousandNineteenStockIncentivePlanMember" order="10350.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_VestingAxis" order="10400.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_VestingAxis" xlink:to="us-gaap_VestingDomain_2" order="10410.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_VestingAxis" xlink:to="us-gaap_VestingDomain" order="10430.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_VestingDomain" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheOneMember" order="10450.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_VestingDomain" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheTwoMember" order="10490.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" order="10500.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2" order="10510.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" order="10530.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" order="10550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PlanNameDomain" xlink:to="ctmx_EarlyExerciseOfEmployeeOptionsMember" order="10670.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="ctmx_EmployeeStockPurchasePlanMember" order="10750.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="ctmx_NonEmployeesMember" order="10950.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" order="10980.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfOutstandingStockMaximum" order="11020.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" order="11060.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardVotingRightsOfCommonStockHoldingPercentage" order="11140.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" order="11180.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" order="11220.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" order="11260.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" order="11490.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" order="11580.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" order="11640.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" order="11700.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" order="11860.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" order="11940.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense" order="12070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" order="12130.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureStockBasedCompensationScheduleOfActivityUnderCompanySStockOptionPlansDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureStockBasedCompensationScheduleOfActivityUnderCompanySStockOptionPlansDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureStockBasedCompensationScheduleOfActivityUnderCompanySStockOptionPlansDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1" xlink:type="locator" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAggregateIntrinsicValueAbstract" xlink:type="locator" xlink:label="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAggregateIntrinsicValueAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1" xlink:type="locator" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" xlink:type="locator" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" xlink:type="locator" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsAuthorizedWeightedAverageExercisePrice" xlink:type="locator" xlink:label="ctmx_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsAuthorizedWeightedAverageExercisePrice" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAuthorized" xlink:type="locator" xlink:label="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAuthorized" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantForfeituresInPeriod" xlink:type="locator" xlink:label="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantForfeituresInPeriod" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantExercisesInPeriod" xlink:type="locator" xlink:label="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantExercisesInPeriod" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantGrantsInPeriod" xlink:type="locator" xlink:label="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantGrantsInPeriod" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAuthorized" xlink:type="locator" xlink:label="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAuthorized" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAbstract" xlink:type="locator" xlink:label="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:type="locator" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AwardTypeAxis" xlink:type="locator" xlink:label="us-gaap_AwardTypeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAbstract" order="10120.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" order="10360.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAbstract" xlink:to="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAuthorized" order="10480.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAbstract" xlink:to="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantGrantsInPeriod" order="10600.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAbstract" xlink:to="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantExercisesInPeriod" order="10720.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantAbstract" xlink:to="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantForfeituresInPeriod" order="10840.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" order="12310.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" order="12550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAuthorized" order="12670.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" order="12790.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" order="12910.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod" order="13030.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" order="14470.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber" order="14590.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" order="14740.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" order="14980.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" order="15220.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice" order="15340.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice" order="15460.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="ctmx_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsAuthorizedWeightedAverageExercisePrice" order="16300.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" order="16900.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice" order="17020.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" order="17170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" order="17410.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" order="17770.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1" order="17890.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAggregateIntrinsicValueAbstract" order="18040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAggregateIntrinsicValueAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" order="18280.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAggregateIntrinsicValueAbstract" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1" order="18640.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ctmx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAggregateIntrinsicValueAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue" order="18760.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureStockBasedCompensationTotalStockBasedCompensationRecognizedDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureStockBasedCompensationTotalStockBasedCompensationRecognizedDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureStockBasedCompensationTotalStockBasedCompensationRecognizedDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:type="locator" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationAbstract" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationAbstract" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_GeneralAndAdministrativeExpenseMember" xlink:type="locator" xlink:label="us-gaap_GeneralAndAdministrativeExpenseMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentExpenseMember" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentExpenseMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:type="locator" xlink:label="us-gaap_IncomeStatementLocationDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:type="locator" xlink:label="us-gaap_IncomeStatementLocationAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_IncomeStatementLocationAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_ResearchAndDevelopmentExpenseMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_GeneralAndAdministrativeExpenseMember" order="10110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationAbstract" order="10140.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationAbstract" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense" order="10260.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureStockBasedCompensationScheduleOfEstimatedFairValueOfEmployeeStockOptionsAndESPPUsingBlackScholesValuationModelDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureStockBasedCompensationScheduleOfEstimatedFairValueOfEmployeeStockOptionsAndESPPUsingBlackScholesValuationModelDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureStockBasedCompensationScheduleOfEstimatedFairValueOfEmployeeStockOptionsAndESPPUsingBlackScholesValuationModelDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:type="locator" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MaximumMember" xlink:type="locator" xlink:label="srt_MaximumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MinimumMember" xlink:type="locator" xlink:label="srt_MinimumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:type="locator" xlink:label="srt_RangeMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:type="locator" xlink:label="srt_RangeAxis" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_EmployeeStockPurchasePlanMember" xlink:type="locator" xlink:label="ctmx_EmployeeStockPurchasePlanMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:type="locator" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AwardTypeAxis" xlink:type="locator" xlink:label="us-gaap_AwardTypeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="ctmx_EmployeeStockPurchasePlanMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="srt_RangeAxis" order="10360.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" order="10390.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" order="10410.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" order="10430.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum" order="10460.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum" order="10580.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum" order="10700.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum" order="10820.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" order="10940.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" order="11060.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureIncomeTaxesAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureIncomeTaxesAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureIncomeTaxesAdditionalInformationDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OpenTaxYear" xlink:type="locator" xlink:label="us-gaap_OpenTaxYear" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestAccrued" xlink:type="locator" xlink:label="us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestAccrued" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" xlink:type="locator" xlink:label="us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_UnrecognizedTaxBenefits" xlink:type="locator" xlink:label="us-gaap_UnrecognizedTaxBenefits" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_PercentageOfChangeInOwnership" xlink:type="locator" xlink:label="ctmx_PercentageOfChangeInOwnership" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_TaxCreditCarryforwardExpirationYear" xlink:type="locator" xlink:label="ctmx_TaxCreditCarryforwardExpirationYear" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TaxCreditCarryforwardAmount" xlink:type="locator" xlink:label="us-gaap_TaxCreditCarryforwardAmount" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_OperatingLossCarryforwardsAmountNotSubjectToExpiration" xlink:type="locator" xlink:label="ctmx_OperatingLossCarryforwardsAmountNotSubjectToExpiration" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_OperatingLossCarryforwardsAmountToExpireIfNotUsed" xlink:type="locator" xlink:label="ctmx_OperatingLossCarryforwardsAmountToExpireIfNotUsed" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_OperatingLossCarryforwardsExpirationYear" xlink:type="locator" xlink:label="ctmx_OperatingLossCarryforwardsExpirationYear" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLossCarryforwards" xlink:type="locator" xlink:label="us-gaap_OperatingLossCarryforwards" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ValuationAllowanceDeferredTaxAssetChangeInAmount" xlink:type="locator" xlink:label="us-gaap_ValuationAllowanceDeferredTaxAssetChangeInAmount" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MaximumMember" xlink:type="locator" xlink:label="srt_MaximumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MinimumMember" xlink:type="locator" xlink:label="srt_MinimumMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:type="locator" xlink:label="srt_RangeMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:type="locator" xlink:label="srt_RangeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchMember" xlink:type="locator" xlink:label="us-gaap_ResearchMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TaxCreditCarryforwardNameDomain" xlink:type="locator" xlink:label="us-gaap_TaxCreditCarryforwardNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TaxCreditCarryforwardNameDomain" xlink:type="locator" xlink:label="us-gaap_TaxCreditCarryforwardNameDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TaxCreditCarryforwardAxis" xlink:type="locator" xlink:label="us-gaap_TaxCreditCarryforwardAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StateAndLocalJurisdictionMember" xlink:type="locator" xlink:label="us-gaap_StateAndLocalJurisdictionMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DomesticCountryMember" xlink:type="locator" xlink:label="us-gaap_DomesticCountryMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain" xlink:type="locator" xlink:label="us-gaap_IncomeTaxAuthorityDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain" xlink:type="locator" xlink:label="us-gaap_IncomeTaxAuthorityDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeTaxAuthorityAxis" xlink:type="locator" xlink:label="us-gaap_IncomeTaxAuthorityAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeTaxContingencyTable" xlink:type="locator" xlink:label="us-gaap_IncomeTaxContingencyTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeTaxContingencyLineItems" xlink:type="locator" xlink:label="us-gaap_IncomeTaxContingencyLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_IncomeTaxContingencyTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_IncomeTaxContingencyTable" xlink:to="us-gaap_IncomeTaxAuthorityAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_IncomeTaxAuthorityAxis" xlink:to="us-gaap_IncomeTaxAuthorityDomain_2" order="10050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IncomeTaxAuthorityAxis" xlink:to="us-gaap_IncomeTaxAuthorityDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxAuthorityDomain" xlink:to="us-gaap_DomesticCountryMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxAuthorityDomain" xlink:to="us-gaap_StateAndLocalJurisdictionMember" order="10110.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_IncomeTaxContingencyTable" xlink:to="us-gaap_TaxCreditCarryforwardAxis" order="10120.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_TaxCreditCarryforwardAxis" xlink:to="us-gaap_TaxCreditCarryforwardNameDomain_2" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TaxCreditCarryforwardAxis" xlink:to="us-gaap_TaxCreditCarryforwardNameDomain" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TaxCreditCarryforwardNameDomain" xlink:to="us-gaap_ResearchMember" order="10170.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_IncomeTaxContingencyTable" xlink:to="srt_RangeAxis" order="10280.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" order="10310.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" order="10330.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" order="10350.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_ValuationAllowanceDeferredTaxAssetChangeInAmount" order="10460.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_OperatingLossCarryforwards" order="10550.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="ctmx_OperatingLossCarryforwardsExpirationYear" order="10610.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="ctmx_OperatingLossCarryforwardsAmountToExpireIfNotUsed" order="10670.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="ctmx_OperatingLossCarryforwardsAmountNotSubjectToExpiration" order="10730.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_TaxCreditCarryforwardAmount" order="10820.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="ctmx_TaxCreditCarryforwardExpirationYear" order="10880.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="ctmx_PercentageOfChangeInOwnership" order="10970.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_UnrecognizedTaxBenefits" order="11020.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" order="11060.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestAccrued" order="11130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_OpenTaxYear" order="11220.00" priority="2" use="optional" />
  </link:definitionLink>
  <link:roleRef roleURI="http://cytomx.com/20191231/taxonomy/role/DisclosureSubsequentEventsAdditionalInformationDetails" xlink:href="ctmx-20191231.xsd#Role_DisclosureSubsequentEventsAdditionalInformationDetails" xlink:type="simple" />
  <link:definitionLink xlink:type="extended" xlink:role="http://cytomx.com/20191231/taxonomy/role/DisclosureSubsequentEventsAdditionalInformationDetails">
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_MilestonePaymentPayable" xlink:type="locator" xlink:label="ctmx_MilestonePaymentPayable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ContingentMilestonePaymentsReceivable" xlink:type="locator" xlink:label="ctmx_ContingentMilestonePaymentsReceivable" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_ImmunoGenIncMember" xlink:type="locator" xlink:label="ctmx_ImmunoGenIncMember" />
    <link:loc xlink:href="ctmx-20191231.xsd#ctmx_BristolMyersSquibbCompanyMember" xlink:type="locator" xlink:label="ctmx_BristolMyersSquibbCompanyMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_CounterpartyNameAxis" xlink:type="locator" xlink:label="srt_CounterpartyNameAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementMember" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventMember" xlink:type="locator" xlink:label="us-gaap_SubsequentEventMember" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:type="locator" xlink:label="us-gaap_SubsequentEventTypeDomain" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:type="locator" xlink:label="us-gaap_SubsequentEventTypeDomain_2" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:type="locator" xlink:label="us-gaap_SubsequentEventTypeAxis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTable" xlink:type="locator" xlink:label="us-gaap_SubsequentEventTable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventLineItems" xlink:type="locator" xlink:label="us-gaap_SubsequentEventLineItems" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="us-gaap_SubsequentEventTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_SubsequentEventTable" xlink:to="us-gaap_SubsequentEventTypeAxis" order="10040.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain_2" order="10050.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain" order="10070.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SubsequentEventTypeDomain" xlink:to="us-gaap_SubsequentEventMember" order="10090.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_SubsequentEventTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10100.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10130.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" order="10150.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_SubsequentEventTable" xlink:to="srt_CounterpartyNameAxis" order="10160.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" order="10190.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_BristolMyersSquibbCompanyMember" order="10210.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="ctmx_ImmunoGenIncMember" order="10390.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="ctmx_ContingentMilestonePaymentsReceivable" order="10420.00" priority="2" use="optional" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="ctmx_MilestonePaymentPayable" order="10470.00" priority="2" use="optional" />
  </link:definitionLink>
</link:linkbase>
