| Champ: | Cristian Garín |
| Runner: |  Facundo Bagnis |
| Score: | 6–4, 6–7(3–7), 7–5 |
| Draw: | 28 |
| Seeds: | 8 |
| Type: | singles doubles |
See main article: 2021 Chile Open.
Cristian Garín defeated Facundo Bagnis in the final, 6–4, 6–7(3–7), 7–5 to capture the men's singles tennis title at the 2021 Chile Open.
Thiago Seyboth Wild was the defending champion, but chose not to defend his title.
The top four seeds received a bye into the second round.