Pada 20 Desember 2019, Zelarayán pindah ke klub [[Major League Soccer]] [[Columbus Crew]] seharga $8 juta.<ref>{{Cite web|url=https://www.columbuscrew.com/post/2019/12/20/columbus-crew-sc-acquires-attacking-midfielder-lucas-zelarayan-designated-player|title=Columbus Crew SC acquires attacking midfielder Lucas Zelarayan as a Designated Player|website=columbuscrew.com|publisher=Columbus Crew|date=20 Desember 2019|access-date=3 Juni 2021}}</ref><ref>{{Cite web |title=Cucho Hernandez transfer: Columbus Crew sign Watford's Colombian striker, paying club-record $10 million fee |url=https://www.cbssports.com/soccer/news/cucho-hernandez-transfer-columbus-crew-sign-watfords-colombian-striker-paying-club-record-10-million-fee/ |access-date=9 Oktober 2022 |website=CBSSports.com }}</ref><ref name=":3">{{Cite web |title=FIFA falló a favor de Belgrano en la causa Zelarayán|url=https://belgranocordoba.com/noticia-belgrano/4181/ |access-date=10 April 2023 |website=belgranocordoba.com}}</ref> Zelarayán melakukan debutnya melawan [[New York City FC]], mencetak gol kemenangan pertandingan pada menit ke-56.<ref>{{Cite web|url=https://www.dispatch.com/sports/20200301/crew-1-nyc-fc-0--lucas-zelarayanrsquos-goal-in-debut-gives-crew-season-opening-win|title=Crew 1, NYC FC 0 {{!}} Lucas Zelarayan's goal in debut gives Crew season-opening win|last=Myers|first=Jacob|website=The Columbus Dispatch|access-date=2 Maret 2020}}</ref> Ia dinobatkan sebagai Pendatang Baru Terbaik liga pada akhir musim reguler 2020. Pada final [[Piala MLS 2020]], Zelarayán mencetak dua gol dan membantu satu gol lainnya dalam kemenangan 3-0 Columbus atas [[Seattle Sounders FC]] untuk membantu mereka memenangkan gelar Piala MLS kedua mereka. Zelarayán dinobatkan sebagai Pemain Paling Berharga Piala MLS setelah penampilannya.<ref>{{Cite web|date=13 Desember 2020|title=Columbus' Zelarayan named MLS Cup MVP|url=https://www.espn.com/soccer/columbus-crew-sc/story/4262117/columbus-crews-lucas-zelarayan-named-mls-cup-mvp|access-date=15 Desember 2020|website=ESPN.com}}</ref>
DuringSelama the 2021musim MLS season2021, Zelarayán scored amencetak total oflima fivegol free-kicktendangan goalsbebas, withdengan twodua ofdi themantaranya comingterjadi indalam onesatu gamepertandingan vsmelawan [[New York City FC]]. BothKedua freegol kicktendangan goalsbebas turnedtersebut outternyata tokrusial be crucial for thebagi Crew, askarena theymereka endedakhirnya upmenang winning 2–12-1, withdengan thetendangan gamebebas winningkemenangan freeterjadi kickpada comingmenit inke-5 thewaktu 5thtambahan minutebabak ofkedua, secondyang halfmembuat stoppageZelarayán time,mendapatkan whichpengakuan earnedsebagai ZelarayánPemain recognition asTerbaik MLS PlayerMinggu of the WeekIni.<ref>{{Cite web|last=mlssoccer|title=Recap: New York City FC 1, Columbus Crew 2|url=https://www.mlssoccer.com/news/recap-new-york-city-fc-1-columbus-crew-2|access-date=9 Desember 2021|website=mlssoccer}}</ref> Zelarayán wasdinobatkan namedsebagai MLSPemain PlayerTerbaik ofMLS theMinggu WeekIni auntuk secondkedua timekalinya inpada themusim 2021 season aftersetelah scoringmencetak 2 goalsgol indalam akemenangan 3–1 victory3-1 againstmelawan [[DC United|D.C. United]].<ref>{{Cite web|url=https://www.mlssoccer.com/news/columbus-crew-s-lucas-zelarayan-named-week-34-mls-player-of-the-week|website=mlssoccer.com|title=Columbus Crew's Lucas Zelarayan named Week 34 MLS Player of the Week|access-date=7 Maret 2022}}</ref> Zelarayán finishedmenyelesaikan thetahun yeartersebut leadingdengan thememimpin clubklub indalam bothhal goalsgol anddan assistsassist withdengan masing-masing twelvedua andbelas sevendan respectivelytujuh.<ref>{{Cite web|last=Murphy|first=Pat|date=19 November 2021|title=The Crew announce 2021 individual end of season awards|url=https://www.massivereport.com/2021/11/19/22791215/columbus-crew-announce-2021-end-of-season-individual-awards-lucas-zelarayan-josh-williams-mls|access-date=9 Desember 2021|website=Massive Report}}</ref> AtPada theakhir end of the seasonmusim, itdiumumkan was announced thatbahwa Zelarayán hadtelah signedmenandatangani aperpanjangan contractkontrak extension with thedengan Crew, keepingyang himmembuatnya withtetap bersama Columbus throughhingga the 2024musim Major League Soccer season2024 withdengan anopsi optionuntuk fortahun 2025.<ref>{{Cite news|last=ColumbusCrew.com|title=Columbus Crew signs midfielder Lucas Zelarayan to new multi-year contract |url=https://www.columbuscrew.com/news/columbus-crew-signs-midfielder-lucas-zelarayan-to-new-multi-year-contract|access-date=9 Desember 2021|website=ColumbusCrew.com}}</ref>
