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.

Men's singles
2021 Mutua Madrid Open
Champion Alexander Zverev
Runner-up Matteo Berrettini
Score6–7(8–10), 6–4, 6–3
Draw56 (8 Q / 4 WC )
Seeds16

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.

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