| Champ: |  Aslan Karatsev |
| Score: | 6–2, 6–4 |
| Draw: | 28 (4 / 3) |
| Seeds: | 8 |
| Before Name: | Kremlin Cup – Men's singles |
| After Name: | Kremlin Cup – Men's singles |
| Before Year: | 2019 |
See main article: article and 2021 Kremlin Cup.
Andrey Rublev was the reigning champion from when the tournament was last held in 2019,[1] but lost to Adrian Mannarino in the second round in a rematch of the 2019 final.
Aslan Karatsev won the title, defeating Marin Čilić in the final, 6–2, 6–4.
The top four seeds received a bye into the second round.