2021 Mutua Madrid Open – Men's singles

Alexander Zverev defeated Matteo Berrettini in the final, 6–7(8–10), 6–4, 6–3 to win the men's singles tennis title at the 2021 Madrid Open. It was Zverev's fourth Masters 1000 title, his first since Madrid 2018, and his 15th career ATP Tour singles title overall. Berrettini was in contention to become the second Italian to be a Masters 1000 champion.

Novak Djokovic was the reigning champion from when the tournament was last held in 2019, but did not participate.

Following the third-round eliminations of Daniil Medvedev and Stefanos Tsitsipas, respectively, a maiden Masters 1000 singles finalist from the bottom half of the draw was guaranteed; Berrettini went on to become that player.

Seeds
The top eight seeds received a bye into the second round. • 🇪🇸 Rafael Nadal (quarterfinals)

• 🇷🇺 Daniil Medvedev (third round)

• 🇦🇹 Dominic Thiem (semifinals)

• Stefanos Tsitsipas (third round)

• 🇩🇪 Alexander Zverev (champion)

• 🇷🇺 Andrey Rublev (third round)

• 🇦🇷 Diego Schwartzman (second round)

• 🇮🇹 Matteo Berrettini (final)

• 🇪🇸 Roberto Bautista Agut (second round)

• 🇪🇸 Pablo Carreño Busta (first round)

• 🇨🇦 Denis Shapovalov (second round)

• 🇵🇱 Hubert Hurkacz (first round)

• 🇧🇬 Grigor Dimitrov (first round)

• 🇮🇹 Jannik Sinner (second round)

• 🇨🇦 Félix Auger-Aliassime (first round)

• Cristian Garín (quarterfinals)

Seeds
• # 🇷🇸 Laslo Đere (first round)

• # 🇯🇵 Yoshihito Nishioka (qualifying competition, retired, lucky loser)

• # 🇦🇺 Jordan Thompson (first round)

• # 🇺🇸 Tennys Sandgren (first round)

• # 🇺🇸 Frances Tiafoe (first round)

• # 🇺🇸 Sebastian Korda (first round)

• # 🇮🇹 Stefano Travaglia (qualifying competition)

• # 🇫🇮 Emil Ruusuvuori (first round)

• # 🇧🇾 Egor Gerasimov (first round)

• # 🇦🇺 Alexei Popyrin (qualified)

• # 🇧🇷 Thiago Monteiro (first round)

• # 🇦🇷 Federico Delbonis (qualified)

• # 🇪🇸 Pablo Andújar (qualified)

• # 🇲🇩 Radu Albot (first round)

Qualifiers
• # 🇦🇷 Federico Delbonis

• # 🇺🇸 Marcos Giron

• # 🇪🇸 Carlos Taberner

• # 🇫🇷 Pierre-Hugues Herbert

• # 🇮🇹 Marco Cecchinato

• # 🇦🇺 Alexei Popyrin

• # 🇪🇸 Pablo Andújar

Lucky loser
• # 🇯🇵 Yoshihito Nishioka

Seeds
The following are the seeded players. Seedings are based on ATP rankings as of 26 April 2021. Rankings and points before are as of 3 May 2021.

Other entrants
The following players received wildcard s into the main draw:
 * 🇪🇸 Carlos Alcaraz
 * 🇪🇸 Pedro Martínez
 * 🇪🇸 Jaume Munar
 * 🇪🇸 Fernando Verdasco

The following players received entry from the qualifying draw:
 * 🇪🇸 Pablo Andújar
 * 🇮🇹 Marco Cecchinato
 * 🇦🇷 Federico Delbonis
 * 🇺🇸 Marcos Giron
 * 🇫🇷 Pierre-Hugues Herbert
 * 🇦🇺 Alexei Popyrin
 * 🇪🇸 Carlos Taberner

The following player received entry as a lucky loser:
 * 🇯🇵 Yoshihito Nishioka

Withdrawals

 * Before the tournament
 * Marin Čilić → replaced by 🇺🇸 Tommy Paul
 * Borna Ćorić → replaced by 🇫🇷 Jérémy Chardy
 * 🇷🇸 Novak Djokovic → replaced by 🇪🇸 Alejandro Davidovich Fokina
 * Roger Federer → replaced by 🇷🇸 Miomir Kecmanović
 * 🇧🇪 David Goffin → replaced by Lloyd Harris
 * 🇫🇷 Gaël Monfils → replaced by 🇦🇷 Guido Pella
 * 🇨🇦 Milos Raonic → replaced by 🇯🇵 Yoshihito Nishioka
 * 🇮🇹 Lorenzo Sonego → replaced by 🇩🇪 Dominik Koepfer
 * Stan Wawrinka → replaced by 🇪🇸 Albert Ramos Viñolas

Retirements

 * Lloyd Harris
 * 🇦🇷 Guido Pella