| Date: | 29 November – 5 December |
| Edition: | 7th |
| Surface: | Clay |
| Location: | São Paulo, Brazil |
| Champs: |  Juan Pablo Ficovich |
| Champd: |  Nicolás Barrientos / Alejandro Gómez |
The 2021 São Paulo Challenger de Tênis was a professional tennis tournament played on clay courts. It was the seventh edition of the tournament which was part of the 2021 ATP Challenger Tour. It took place in São Paulo, Brazil between 29 November and 5 December 2021.
| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
 Bolivia, Plurination;al State of | Hugo Dellien | 119 | 2 | |
 Brazil | Thiago Seyboth Wild | 132 | 3 | |
| Argentina | Juan Ignacio Londero | 144 | 4 | |
| Nicolás Jarry | 160 | 5 | ||
| Brazil | Felipe Meligeni Alves | 180 | 6 | |
| Argentina | Nicolás Kicker | 236 | 7 | |
| Argentina | Pedro Cachin | 258 | 8 |
The following players received wildcards into the singles main draw:
Mateus Alves Oscar José Gutierrez Gustavo HeideThe following players received entry into the singles main draw as alternates:
Daniel Dutra da Silva Alejandro González Facundo Juárez Gilbert Klier JúniorThe following players received entry from the qualifying draw:
Luciano Darderi Igor Marcondes Gonzalo Villanueva Matías ZukasThe following player received entry as a lucky loser:
See main article: 2021 São Paulo Challenger de Tênis – Singles.
Juan Pablo Ficovich def. Luciano Darderi 6–3, 7–5.See main article: 2021 São Paulo Challenger de Tênis – Doubles.
Nicolás Barrientos / Alejandro Gómez def. Rafael Matos / Felipe Meligeni Alves Walkover.