Stefanos Tsitsipas defeated Andrey Rublev in the final, 6–3, 6–3 to win the singles tennis title at the 2021 Monte-Carlo Masters.

Rublev was also in contention for his maiden Masters 1000 title.

[1] Fabio Fognini was the defending champion from when the tournament was last held in 2019,[2] but lost to Casper Ruud in the quarterfinals.

[3] The top eight seeds received a bye into the second round.

Click on the seed number of a player to go to their draw section.