| Champ: |  Lorenzo Sonego |
| Runner: |  Laslo Đere |
| Score: | 2–6, 7–6(7–5), 6–4 |
| Draw: | 28 |
| Seeds: | 8 |
| Type: | singles doubles |
| Before Name: | Forte Village Sardegna Open |
| After Year: | 2023 |
See main article: article and 2021 Sardegna Open.
Lorenzo Sonego defeated defending champion Laslo Đere in the final, 2–6, 7–6(7–5), 6–4 to win the men's singles title at the 2021 Sardegna Open. With the victory, Sonego became the first Italian in 15 years to capture an ATP Tour title on home soil.
The top four seeds received a bye into the second round.