| Champ: |  Diego Schwartzman |
| Runner: | Francisco Cerúndolo |
| Score: | 6–1, 6–2 |
| Draw: | 28 (4 / 3) |
| Seeds: | 8 |
| Type: | singles doubles |
| Main Name: | ATP Buenos Aires |
See main article: article and 2021 Argentina Open.
Diego Schwartzman defeated Francisco Cerúndolo in the final, 6–1, 6–2 to win the men's singles tennis title at the 2021 Argentina Open.
Casper Ruud was the defending champion,[1] but chose not to participate.
The top four seeds receive a bye into the second round.