| Champ: |  Marcel Granollers Horacio Zeballos |
| Runner: | Nikola Mektić Mate Pavić |
| Score: | 1–6, 6–3, [10–8] |
| Before Name: | Mutua Madrid Open – Men's doubles |
| After Name: | Mutua Madrid Open – Men's doubles |
| Before Year: | 2019 |
See main article: article and 2021 Mutua Madrid Open.
Marcel Granollers and Horacio Zeballos defeated Nikola Mektić and Mate Pavić in the final, 1–6, 6–3, [10–8], to win the men's doubles tennis title at the 2021 Madrid Open. It was the third-seeded duo's third ATP Tour Masters 1000 doubles title together. Mektić and Pavić were contending to be the first doubles team in five years to win a season's first three Masters 1000 events.[1]
Jean-Julien Rojer and Horia Tecău were the defending champions from when the tournament was last held in 2019,[2] though they returned to defend their title with different partners. Rojer partnered with Marcelo Melo but lost in the second round to Tim Pütz and Alexander Zverev. Tecău partnered with Kevin Krawietz and lost to Ivan Dodig and Filip Polášek, also in the second round.[3]
Pavić and Robert Farah were in contention for the ATP No. 1 doubles ranking at the start of the tournament. Pavić retained the top ranking after Farah lost in the second round.
The top four seeds received a bye into the second round.
The following pairs received wildcards into the doubles main draw:
Alejandro Davidovich Fokina / Fernando Verdasco Marc López / Jaume MunarThe following pair received entry into the doubles draw as alternate:
Márton Fucsovics / 
Casper Ruud Alejandro Davidovich Fokina / Fernando Verdasco → replaced by Raven Klaasen / 
Ben McLachlan
Colombia
Slovakia
United Kingdom
France
Poland
Brazil