<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2021 Workiva-->
<!--r:40d01a35-9489-4370-9a59-80cafe8981b7,g:c2f5195e-ac99-40f1-838a-2eeffb896a31-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" 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:roleRef roleURI="http://www.nautilus.bio/role/Cover" xlink:type="simple" xlink:href="naut-20210810.xsd#Cover"/>
  <link:presentationLink xlink:role="http://www.nautilus.bio/role/Cover" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_CoverAbstract"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentType_71ac9603-35c8-499b-9085-aa22f92f9899" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_DocumentType"/>
    <link:presentationArc order="1" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_DocumentType_71ac9603-35c8-499b-9085-aa22f92f9899" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentPeriodEndDate_b4253f67-9a40-48ab-b1a1-ebf69c14389d" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_DocumentPeriodEndDate"/>
    <link:presentationArc order="2" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_DocumentPeriodEndDate_b4253f67-9a40-48ab-b1a1-ebf69c14389d" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityRegistrantName_53b3afa5-a02e-4ce6-a215-02ff520eb70b" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityRegistrantName"/>
    <link:presentationArc order="3" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityRegistrantName_53b3afa5-a02e-4ce6-a215-02ff520eb70b" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityIncorporationStateCountryCode_3d02bde8-50d4-404d-b85d-06d61b443ace" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityIncorporationStateCountryCode"/>
    <link:presentationArc order="4" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityIncorporationStateCountryCode_3d02bde8-50d4-404d-b85d-06d61b443ace" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFileNumber_9e4a23b2-36bd-44c4-8d71-23f607fc158f" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityFileNumber"/>
    <link:presentationArc order="5" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityFileNumber_9e4a23b2-36bd-44c4-8d71-23f607fc158f" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityTaxIdentificationNumber_582aa24c-3690-4be3-bc47-63a7200e290a" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityTaxIdentificationNumber"/>
    <link:presentationArc order="6" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityTaxIdentificationNumber_582aa24c-3690-4be3-bc47-63a7200e290a" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressAddressLine1_f5ace88e-36bc-40a2-9fbf-4abef7f46ec2" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityAddressAddressLine1"/>
    <link:presentationArc order="7" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityAddressAddressLine1_f5ace88e-36bc-40a2-9fbf-4abef7f46ec2" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressCityOrTown_8b5330c5-e549-4557-8e23-ee85d75e86b7" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityAddressCityOrTown"/>
    <link:presentationArc order="8" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityAddressCityOrTown_8b5330c5-e549-4557-8e23-ee85d75e86b7" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressStateOrProvince_49035656-d783-4390-b073-cdda81919117" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityAddressStateOrProvince"/>
    <link:presentationArc order="9" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityAddressStateOrProvince_49035656-d783-4390-b073-cdda81919117" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressPostalZipCode_5a53b700-a333-4e8a-b8c4-a0de379cc108" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityAddressPostalZipCode"/>
    <link:presentationArc order="10" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityAddressPostalZipCode_5a53b700-a333-4e8a-b8c4-a0de379cc108" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CityAreaCode_c1eb866f-03aa-4481-945c-8215df02f52f" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_CityAreaCode"/>
    <link:presentationArc order="11" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_CityAreaCode_c1eb866f-03aa-4481-945c-8215df02f52f" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LocalPhoneNumber_c8fd67f9-2da0-4ed3-babd-262247bf215c" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_LocalPhoneNumber"/>
    <link:presentationArc order="12" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_LocalPhoneNumber_c8fd67f9-2da0-4ed3-babd-262247bf215c" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_WrittenCommunications_6a7f8985-b553-4caf-95e0-e287df4c6976" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_WrittenCommunications"/>
    <link:presentationArc order="13" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_WrittenCommunications_6a7f8985-b553-4caf-95e0-e287df4c6976" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SolicitingMaterial_17a59a0a-0b39-4b1b-a29b-8931cc3e52a9" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_SolicitingMaterial"/>
    <link:presentationArc order="14" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_SolicitingMaterial_17a59a0a-0b39-4b1b-a29b-8931cc3e52a9" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_PreCommencementTenderOffer_5a465dc8-17c6-4951-9031-9ce5ed74a247" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_PreCommencementTenderOffer"/>
    <link:presentationArc order="15" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_PreCommencementTenderOffer_5a465dc8-17c6-4951-9031-9ce5ed74a247" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_PreCommencementIssuerTenderOffer_b8c0b876-b8e2-42bb-ac41-178f24b6f97c" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_PreCommencementIssuerTenderOffer"/>
    <link:presentationArc order="16" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_PreCommencementIssuerTenderOffer_b8c0b876-b8e2-42bb-ac41-178f24b6f97c" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_Security12bTitle_7dc03a61-60f2-440a-bb4c-a455d27a0a5c" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_Security12bTitle"/>
    <link:presentationArc order="17" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_Security12bTitle_7dc03a61-60f2-440a-bb4c-a455d27a0a5c" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_TradingSymbol_26d19f8b-8ac5-4474-bfc1-fa1aacca33f7" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_TradingSymbol"/>
    <link:presentationArc order="18" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_TradingSymbol_26d19f8b-8ac5-4474-bfc1-fa1aacca33f7" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SecurityExchangeName_2ec4a3be-e925-4458-be2d-4e63cc51fc5e" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_SecurityExchangeName"/>
    <link:presentationArc order="19" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_SecurityExchangeName_2ec4a3be-e925-4458-be2d-4e63cc51fc5e" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityEmergingGrowthCompany_f3cbb61f-6411-446e-8546-bc9f68438622" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityEmergingGrowthCompany"/>
    <link:presentationArc order="20" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityEmergingGrowthCompany_f3cbb61f-6411-446e-8546-bc9f68438622" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityExTransitionPeriod_f7473433-4147-4976-9845-701276418664" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityExTransitionPeriod"/>
    <link:presentationArc order="21" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityExTransitionPeriod_f7473433-4147-4976-9845-701276418664" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCentralIndexKey_e8d7d635-c627-4d4e-9fc3-d291b234e014" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityCentralIndexKey"/>
    <link:presentationArc order="22" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_EntityCentralIndexKey_e8d7d635-c627-4d4e-9fc3-d291b234e014" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AmendmentFlag_4c2665b3-d706-477b-b8ed-dfae842ce02c" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_AmendmentFlag"/>
    <link:presentationArc order="23" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="loc_dei_CoverAbstract_49d1891d-cf7c-4aa7-97fa-b8476fb6ba60" xlink:to="loc_dei_AmendmentFlag_4c2665b3-d706-477b-b8ed-dfae842ce02c" xlink:type="arc" preferredLabel="http://www.xbrl.org/2003/role/terseLabel"/>
  </link:presentationLink>
</link:linkbase>
