<?xml version="1.0" encoding="US-ASCII"?>
<!-- DFIN New ActiveDisclosure (SM) XBRL Schema Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date :2022-08-04T11:19:15.5796+00:00 -->
<!-- Copyright (c) 2022 Donnelly Financial Solutions, Inc. All Rights Reserved. -->
<xsd:schema targetNamespace="http://cytomx.com/20220630" attributeFormDefault="unqualified" elementFormDefault="qualified" xmlns:country="http://xbrl.sec.gov/country/2022" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:enum2="http://xbrl.org/2020/extensible-enumerations-2.0" xmlns:ctmx="http://cytomx.com/20220630" xmlns:srt="http://fasb.org/srt/2022" xmlns:xsd="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:us-gaap="http://fasb.org/us-gaap/2022" xmlns:dei="http://xbrl.sec.gov/dei/2022" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:xlink="http://www.w3.org/1999/xlink">
  <xsd:import schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd" namespace="http://www.xbrl.org/2003/instance"/>
  <xsd:import schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" namespace="http://www.xbrl.org/2003/linkbase"/>
  <xsd:import schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd" namespace="http://xbrl.org/2005/xbrldt"/>
  <xsd:import schemaLocation="https://www.xbrl.org/2020/extensible-enumerations-2.0.xsd" namespace="http://xbrl.org/2020/extensible-enumerations-2.0"/>
  <xsd:import schemaLocation="https://xbrl.sec.gov/dei/2022/dei-2022.xsd" namespace="http://xbrl.sec.gov/dei/2022"/>
  <xsd:import schemaLocation="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd" namespace="http://fasb.org/us-gaap/2022"/>
  <xsd:import schemaLocation="https://xbrl.sec.gov/country/2022/country-2022.xsd" namespace="http://xbrl.sec.gov/country/2022"/>
  <xsd:import schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/types.xsd" namespace="http://www.xbrl.org/dtr/type/2020-01-21"/>
  <xsd:import schemaLocation="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd" namespace="http://fasb.org/srt/2022"/>
  <xsd:annotation>
    <xsd:appinfo>
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="ctmx-20220630_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:title="Labels link" xlink:type="simple"/>
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="ctmx-20220630_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:title="Presentation link" xlink:type="simple"/>
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="ctmx-20220630_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:title="Definition link" xlink:type="simple"/>
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="ctmx-20220630_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:title="Calculation link" xlink:type="simple"/>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DocumentDocumentAndEntityInformation" id="DocumentDocumentAndEntityInformation">
        <link:definition>100000 - Document - Document and Entity Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_StatementCONDENSEDBALANCESHEETS" id="Role_StatementCONDENSEDBALANCESHEETS">
        <link:definition>100010 - Statement - CONDENSED BALANCE SHEETS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureFairValueMeasurementsAndInvestmentsScheduleOfInvestmentsSubjectToFairValueMeasurementsOnARecurringBasisDetails2" id="DisclosureFairValueMeasurementsAndInvestmentsScheduleOfInvestmentsSubjectToFairValueMeasurementsOnARecurringBasisDetails2">
        <link:definition>100020 - Disclosure - Fair Value Measurements and Investments - Schedule of Investments Subject to Fair Value Measurements on a Recurring Basis (Details) 2</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_StatementCONDENSEDBALANCESHEETSParenthetical" id="Role_StatementCONDENSEDBALANCESHEETSParenthetical">
        <link:definition>100030 - Statement - CONDENSED BALANCE SHEETS (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_StatementCONDENSEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" id="Role_StatementCONDENSEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS">
        <link:definition>100040 - Statement - CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/StatementCondensedStatementsOfStockholdersEquity" id="StatementCondensedStatementsOfStockholdersEquity">
        <link:definition>100050 - Statement - CONDENSED STATEMENTS OF STOCKHOLDERS' EQUITY</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_StatementCONDENSEDSTATEMENTSOFCASHFLOWS" id="Role_StatementCONDENSEDSTATEMENTSOFCASHFLOWS">
        <link:definition>100060 - Statement - CONDENSED STATEMENTS OF CASH FLOWS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureDescriptionOfBusiness" id="Role_DisclosureDescriptionOfBusiness">
        <link:definition>100070 - Disclosure - Description of the Business</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPolicies" id="Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPolicies">
        <link:definition>100080 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureNetLossPerShare" id="Role_DisclosureNetLossPerShare">
        <link:definition>100090 - Disclosure - Net Loss Per Share</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureFairValueMeasurementsAndInvestments" id="DisclosureFairValueMeasurementsAndInvestments">
        <link:definition>100100 - Disclosure - Fair Value Measurements and Investments</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureAccruedLiabilities" id="Role_DisclosureAccruedLiabilities">
        <link:definition>100110 - Disclosure - Accrued Liabilities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureResearchAndCollaborationAgreements" id="Role_DisclosureResearchAndCollaborationAgreements">
        <link:definition>100120 - Disclosure - Research and Collaboration Agreements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureCommonStock" id="Role_DisclosureCommonStock">
        <link:definition>100130 - Disclosure - Common Stock</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureStockBasedCompensation" id="Role_DisclosureStockBasedCompensation">
        <link:definition>100140 - Disclosure - Stock-Based Compensation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureCommitmentsAndContingencies" id="Role_DisclosureCommitmentsAndContingencies">
        <link:definition>100150 - Disclosure - Commitments and Contingencies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureIncomeTaxes1" id="DisclosureIncomeTaxes1">
        <link:definition>100160 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureSubsequentEvent" id="DisclosureSubsequentEvent">
        <link:definition>100170 - Disclosure - Subsequent Event</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesPolicies" id="Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesPolicies">
        <link:definition>100180 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesTables" id="Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesTables">
        <link:definition>100190 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureNetLossPerShareTables" id="Role_DisclosureNetLossPerShareTables">
        <link:definition>100200 - Disclosure - Net Loss Per Share (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureFairValueMeasurementsAndInvestmentsTables" id="DisclosureFairValueMeasurementsAndInvestmentsTables">
        <link:definition>100210 - Disclosure - Fair Value Measurements and Investments (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureAccruedLiabilitiesTables" id="Role_DisclosureAccruedLiabilitiesTables">
        <link:definition>100220 - Disclosure - Accrued Liabilities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureResearchAndCollaborationAgreementsTables" id="Role_DisclosureResearchAndCollaborationAgreementsTables">
        <link:definition>100230 - Disclosure -  Research and Collaboration Agreements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureStockBasedCompensationTables" id="Role_DisclosureStockBasedCompensationTables">
        <link:definition>100240 - Disclosure - Stock-Based Compensation (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesSummaryOfReconciliationOfCashCashEquivalentsAndRestrictedCashDetails" id="Role_DisclosureBasisOfPresentationAndSummaryOfSignificantAccountingPoliciesSummaryOfReconciliationOfCashCashEquivalentsAndRestrictedCashDetails">
        <link:definition>100250 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Summary of Reconciliation of Cash, Cash Equivalents, and Restricted Cash (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureNetLossPerShareSummaryOfPotentiallyDilutiveSecuritiesExcludedFromComputationOfDilutedNetLossPerShareDetails" id="Role_DisclosureNetLossPerShareSummaryOfPotentiallyDilutiveSecuritiesExcludedFromComputationOfDilutedNetLossPerShareDetails">
        <link:definition>100260 - Disclosure - Net Loss Per Share - Summary of Potentially Dilutive Securities Excluded from Computation of Diluted Net Loss Per Share (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureFairValueMeasurementsAndInvestmentsScheduleOfInvestmentsSubjectToFairValueMeasurementsOnARecurringBasisDetails" id="DisclosureFairValueMeasurementsAndInvestmentsScheduleOfInvestmentsSubjectToFairValueMeasurementsOnARecurringBasisDetails">
        <link:definition>100270 - Disclosure - Fair Value Measurements and Investments - Schedule of Investments Subject to Fair Value Measurements on a Recurring Basis (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureFairValueMeasurementsAndInvestmentsAdditionalInformationDetails" id="DisclosureFairValueMeasurementsAndInvestmentsAdditionalInformationDetails">
        <link:definition>100280 - Disclosure - Fair Value Measurements and Investments - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureAccruedLiabilitiesSummaryOfAccruedLiabilitiesDetails" id="Role_DisclosureAccruedLiabilitiesSummaryOfAccruedLiabilitiesDetails">
        <link:definition>100290 - Disclosure - Accrued Liabilities - Summary of Accrued Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureResearchAndCollaborationAgreementsScheduleOfRevenueByCollaborationPartnersDetails" id="Role_DisclosureResearchAndCollaborationAgreementsScheduleOfRevenueByCollaborationPartnersDetails">
        <link:definition>100300 - Disclosure - Research and Collaboration Agreements - Schedule of Revenue by Collaboration Partners (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails" id="Role_DisclosureResearchAndCollaborationAgreementsAbbvieIrelandUnlimitedCompanyAdditionalInformationDetails">
        <link:definition>100310 - Disclosure - Research and Collaboration Agreements - AbbVie Ireland Unlimited Company - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureResearchAndCollaborationAgreementsAmgenIncAdditionalInformationDetails" id="Role_DisclosureResearchAndCollaborationAgreementsAmgenIncAdditionalInformationDetails">
        <link:definition>100320 - Disclosure - Research and Collaboration Agreements - Amgen, Inc - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureResearchAndCollaborationAgreementsAstellasPharmaIncAdditionalInformationDetails" id="Role_DisclosureResearchAndCollaborationAgreementsAstellasPharmaIncAdditionalInformationDetails">
        <link:definition>100330 - Disclosure - Research and Collaboration Agreements - Astellas Pharma Inc - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureResearchAndCollaborationAgreementsBristolMyersSquibbCompanyAdditionalInformationDetails" id="Role_DisclosureResearchAndCollaborationAgreementsBristolMyersSquibbCompanyAdditionalInformationDetails">
        <link:definition>100340 - Disclosure - Research and Collaboration Agreements - Bristol-Myers Squibb Company - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureResearchAndCollaborationAgreementsSummaryOfContractLiabilitiesDetails" id="Role_DisclosureResearchAndCollaborationAgreementsSummaryOfContractLiabilitiesDetails">
        <link:definition>100350 - Disclosure - Research and Collaboration Agreements - Summary of Contract Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureResearchAndCollaborationAgreementsContractLiabilitiesAdditionalInformationDetails" id="Role_DisclosureResearchAndCollaborationAgreementsContractLiabilitiesAdditionalInformationDetails">
        <link:definition>100360 - Disclosure - Research and Collaboration Agreements - Contract Liabilities - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureStockBasedCompensationScheduleOfActivitiesUnderCompanySStockOptionPlansDetails" id="Role_DisclosureStockBasedCompensationScheduleOfActivitiesUnderCompanySStockOptionPlansDetails">
        <link:definition>100370 - Disclosure - Stock-Based Compensation - Schedule of Activities Under Company's Stock Option Plans (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureStockbasedCompensationScheduleOfCompanysTrsuActivitiesDetails" id="DisclosureStockbasedCompensationScheduleOfCompanysTrsuActivitiesDetails">
        <link:definition>100380 - Disclosure - Stock-Based Compensation - Schedule of Company's TRSU Activities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureStockbasedCompensationScheduleOfActivitiesForCompanysPsusDetails" id="DisclosureStockbasedCompensationScheduleOfActivitiesForCompanysPsusDetails">
        <link:definition>100390 - Disclosure - Stock-Based Compensation - Schedule of Activities for Company's PSUs (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/Role_DisclosureStockBasedCompensationTotalStockBasedCompensationRecognizedDetails" id="Role_DisclosureStockBasedCompensationTotalStockBasedCompensationRecognizedDetails">
        <link:definition>100400 - Disclosure - Stock-Based Compensation - Total Stock-based Compensation Recognized (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureStockbasedCompensationAdditionalInformationDetails" id="DisclosureStockbasedCompensationAdditionalInformationDetails">
        <link:definition>100410 - Disclosure - Stock-Based Compensation - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureCommitmentsAndContingenciesAdditionalInformationDetails" id="DisclosureCommitmentsAndContingenciesAdditionalInformationDetails">
        <link:definition>100420 - Disclosure - Commitments and Contingencies - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://cytomx.com/20220630/taxonomy/role/DisclosureSubsequentEventAdditionalInformationDetails" id="DisclosureSubsequentEventAdditionalInformationDetails">
        <link:definition>100430 - Disclosure - Subsequent Event - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xsd:appinfo>
  </xsd:annotation>
  <xsd:element id="ctmx_AccruedResearchAndClinicalCurrent" name="AccruedResearchAndClinicalCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="ctmx_AggregateCollaborationTransactionAmount" name="AggregateCollaborationTransactionAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="ctmx_CashCashEquivalentsAndInvestments" name="CashCashEquivalentsAndInvestments" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_CashCashEquivalentsAndInvestmentsAccumulatedGrossUnrealizedGainBeforeTax" name="CashCashEquivalentsAndInvestmentsAccumulatedGrossUnrealizedGainBeforeTax" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="ctmx_CashCashEquivalentsAndInvestmentsAmortizedCostBasis" name="CashCashEquivalentsAndInvestmentsAmortizedCostBasis" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_CashCashEquivalentsAndShortTermInvestmentsAccumulatedGrossUnrealizedLossBeforeTax" name="CashCashEquivalentsAndShortTermInvestmentsAccumulatedGrossUnrealizedLossBeforeTax" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_CashCashEquivalentsAndShortTermInvestmentsAmortizedCostBasis" name="CashCashEquivalentsAndShortTermInvestmentsAmortizedCostBasis" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_CollaborationTargetResearchTerm" name="CollaborationTargetResearchTerm" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_CommonStockSharesIssuableUnderAgreement" name="CommonStockSharesIssuableUnderAgreement" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_ContingentMilestonePaymentsReceivable" name="ContingentMilestonePaymentsReceivable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_ContingentPaymentsPayableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" name="ContingentPaymentsPayableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="ctmx_ContingentPaymentsReceivableProfitSplitOnSales" name="ContingentPaymentsReceivableProfitSplitOnSales" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_ContingentPaymentsReceivableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" name="ContingentPaymentsReceivableUponAchievingDevelopmentRegulatoryAndCommercialMilestones" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_ContractWithCustomerLiabilityAdditions" name="ContractWithCustomerLiabilityAdditions" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="ctmx_DebtSecuritiesAvailableForSaleMaturityPeriod" name="DebtSecuritiesAvailableForSaleMaturityPeriod" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_DeferredRevenueRecognitionMaturityYear" name="DeferredRevenueRecognitionMaturityYear" type="dtr-types:gYearListItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_DepreciationAndAmortizationExcludingAmortizationOfIntangibleAssets" name="DepreciationAndAmortizationExcludingAmortizationOfIntangibleAssets" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_EstimatedResearchServiceTerminationDate" name="EstimatedResearchServiceTerminationDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_ExtensionOfResearchTermForEachCollaborationTarget" name="ExtensionOfResearchTermForEachCollaborationTarget" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_IncreaseDecreaseInAccruedAndOtherLiabilitiesNoncurrent" name="IncreaseDecreaseInAccruedAndOtherLiabilitiesNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_IncrementsOfExtendedCollaborationTargetResearchTimes" name="IncrementsOfExtendedCollaborationTargetResearchTimes" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_LossContingencyAnswerAffirmativeDefensesAndCounterclaimsFilingDate" name="LossContingencyAnswerAffirmativeDefensesAndCounterclaimsFilingDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_LossContingencyAnswerAndCounterclaimsByPlaintiffFilingDate" name="LossContingencyAnswerAndCounterclaimsByPlaintiffFilingDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_MilestonePaymentReceived" name="MilestonePaymentReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_MilestonePaymentsReceivedFromRevenueRecognizedDuringPeriod" name="MilestonePaymentsReceivedFromRevenueRecognizedDuringPeriod" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_NoncashLeaseExpense" name="NoncashLeaseExpense" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="ctmx_NumberOfAdditionalCollaborationTarget" name="NumberOfAdditionalCollaborationTarget" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_NumberOfCollaborationAgreements" name="NumberOfCollaborationAgreements" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_NumberOfCollaborationTarget" name="NumberOfCollaborationTarget" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_NumberOfOncologyTarget" name="NumberOfOncologyTarget" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_NumberOfResearchTargetsSelected" name="NumberOfResearchTargetsSelected" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_NumberOfTargets" name="NumberOfTargets" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_NumberOfTargetsSelected" name="NumberOfTargetsSelected" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_PercentageOfNetIncomeOrNetLossesRelatedToDevelopmentAndCommercializationCosts" name="PercentageOfNetIncomeOrNetLossesRelatedToDevelopmentAndCommercializationCosts" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_PeriodOfNominationOfAdditionalTarget" name="PeriodOfNominationOfAdditionalTarget" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_ProfitShareUponExerciseOfCoDevelopmentOption" name="ProfitShareUponExerciseOfCoDevelopmentOption" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_ResearchAndDevelopmentServiceFees" name="ResearchAndDevelopmentServiceFees" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_RightToExpandNumberOfAdditionalCollaborationTarget" name="RightToExpandNumberOfAdditionalCollaborationTarget" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_UpfrontFeeReceived" name="UpfrontFeeReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="ctmx_AbbVieIrelandUnlimitedCompanyMember" name="AbbVieIrelandUnlimitedCompanyMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_AchievingAdditionalTargetsMember" name="AchievingAdditionalTargetsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_AdditionalContingentPaymentsMember" name="AdditionalContingentPaymentsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_AmgenIncMember" name="AmgenIncMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_AmgenOtherProductsMember" name="AmgenOtherProductsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_AmgenProductsMember" name="AmgenProductsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_AstellasPharmaIncMember" name="AstellasPharmaIncMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_BristolMyersSquibbCompanyMember" name="BristolMyersSquibbCompanyMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_CD71AgreementMember" name="CD71AgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_CollaborationAndLicenseAgreementMember" name="CollaborationAndLicenseAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_DevelopmentRegulatoryAndCommercialMilestonePaymentsMember" name="DevelopmentRegulatoryAndCommercialMilestonePaymentsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_DiscoveryAgreementMember" name="DiscoveryAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_EGFRProductsMember" name="EGFRProductsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_EmployeeStockPurchasePlanMember" name="EmployeeStockPurchasePlanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_MoneyMarketFundsIncludedInRestrictedCashMember" name="MoneyMarketFundsIncludedInRestrictedCashMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_OptionsAndESPPToPurchaseCommonStockMember" name="OptionsAndESPPToPurchaseCommonStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_PatentInfringementLawsuitMember" name="PatentInfringementLawsuitMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_PerformanceBasedRestrictedStockUnitsMember" name="PerformanceBasedRestrictedStockUnitsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_SecondTargetMember" name="SecondTargetMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_SecondTargetUnderDiscoveryAgreementMember" name="SecondTargetUnderDiscoveryAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_ThirdAndFourthTargetsMember" name="ThirdAndFourthTargetsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_TimeBasedRestrictedStockUnitsMember" name="TimeBasedRestrictedStockUnitsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_TrancheOneMember" name="TrancheOneMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_TrancheTwoMember" name="TrancheTwoMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="ctmx_UnauditedInterimFinancialInformationPolicyTextBlock" name="UnauditedInterimFinancialInformationPolicyTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_ScheduleOfCashCashEquivalentsAndRestrictedCashTableTextBlock" name="ScheduleOfCashCashEquivalentsAndRestrictedCashTableTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_CommonStockTextBlock" name="CommonStockTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="ctmx_ResearchAndCollaborationAgreementsTextBlock" name="ResearchAndCollaborationAgreementsTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
</xsd:schema>
