| Champ: | Marin Čilić |
| Runner: |  Félix Auger-Aliassime |
| Score: | 7–6(7–2), 6–3 |
| Draw: | 28 |
| Seeds: | 8 |
| Type: | singles doubles |
| Before Year: | 2019 |
| Before Name: | MercedesCup – Singles |
| After Name: | BOSS Open – Singles |
| Main Name: | Stuttgart Open |
See main article: article and 2021 MercedesCup.
Marin Čilić defeated Félix Auger-Aliassime in the final, 7–6(7–2), 6–3 to win the singles tennis title at the 2021 Stuttgart Open. It was Čilić's 19th career ATP Tour singles title, his first in three years, and he did not drop a set en route to the victory. The No. 47-ranked, 32-year-old Čilić also became the lowest-ranked winner since Juan Carlos Ferrero in 2011 and the third-oldest champion in tournament history. Defending finalist Auger-Aliassime was contesting for his first career singles title in his eighth final.[1]
Matteo Berrettini was the reigning champion from when the event was last held in 2019,[2] but he could not participate as he was still competing at the French Open upon the beginning of the tournament.
The top four seeds received a bye into the second round.