Lukáš Dlouhý and Leander Paes were the defending champions, but lost in the first round to Martin Damm and Filip Polášek 6–7(7–9), 6–3, 6–4.
Julian Knowle and Jürgen Melzer were the defending champions, but they lost to Marcelo Melo and Bruno Soares in the quarterfinal.
Eric Butorac and Jean-Julien Rojer won in the final 6–3, 6–2, against Andreas Seppi and Dmitry Tursunov.
John Isner and Sam Querrey were the defending champions, but they lost to Kevin Anderson and Ashley Fisher in the quarterfinals.
Max Mirnyi and Daniel Nestor won this tournament. They defeated Eric Butorac and Jean-Julien Rojer 6–2, 6–7(6–8), [10–3] in the final.
Daniel Nestor and Nenad Zimonjić were the defending champions, but decided not to participate together. Nestor partnered Max Mirnyi, while Zimonjić teamed up with Michaël Llodra. Mirnyi and Nestor defeated Zimonjić and Llodra in the semifinals, 7–6(7–4), 7–6(7–5). In the final, they won against Juan Sebastián Cabal and Eduardo Schwank 7–6(7–3), 3–6, 6–4 for their first Grand Slam doubles title as a team.
Bob and Mike Bryan were the defending champions, but lost in the first round to Ivo Karlović and Frank Moser. It marked the first time the Bryan brothers lost in the first round of a Grand Slam tournament since the 2001 Australian Open, a span of 42 Grand Slam tournaments, and their first opening round loss at the US Open since 1999.
Lukáš Dlouhý and Paul Hanley were the defending champions but decided not to participate together.
Dlouhý played alongside Marcelo Melo, while Hanley partnered up with Jamie Murray.
Daniele Bracciali and František Čermák were the defending champions but Bracciali decided not to participate here, instead of 2012 Aegon International.
Čermák played alongside Filip Polášek but lost in the Quarterfinals.
Robert Lindstedt and Horia Tecău won the title by beating Juan Sebastián Cabal and Dmitry Tursunov 6–3, 7–6(7–1) in the final.
Max Mirnyi and Daniel Nestor were the defending champions, but chose not to compete together. Mirnyi competed with Horia Tecău, but lost in the second round to Michaël Llodra and Nicolas Mahut, while Nestor competed with Robert Lindstedt, losing in the second round to Jonathan Dasnières de Veigy and Florent Serra.
Aisam-ul-Haq Qureshi and Jean-Julien Rojer were the defending champions, but lost in the first round to Kei Nishikori and Milos Raonic.
Santiago González and Scott Lipsky won the title, defeating Daniele Bracciali and Jonathan Erlich in the final, 6–2, 7–6(7–3).
Julian Knowle and Filip Polášek were the defending champions, but Polášek decided not to participate. Knowle played alongside Johan Brunström, but they lost in the quarterfinals to Marcelo Demoliner and Purav Raja.
Aisam-ul-Haq Qureshi and Jean-Julien Rojer were the defending champions, but Qureshi chose not to participate this year. Rojer played alongside Horia Tecău, but lost in the first round to Grigor Dimitrov and Pierre-Hugues Herbert.
Eric Butorac and Raven Klaasen won the title, defeating Treat Huey and Jack Sock in the final, 6-4, 6-3.
Michaël Llodra and Nicolas Mahut were the defending champions, but Llodra chose not to participate this year. Mahut played alongside Vasek Pospisil, but lost in the first round to Julien Benneteau and Édouard Roger-Vasselin.
Jean-Julien Rojer and Horia Tecău won the title, defeating Jamie Murray and John Peers in the final, 3–6, 6–3, [10–8].
Jean-Julien Rojer and Horia Tecău are the defending champions, but lost to Vasek Pospisil and Jack Sock in the semifinals.
Daniel Nestor and Édouard Roger-Vasselin were the defending champions, but chose not to compete together. Nestor played alongside Vasek Pospisil, but lost in the semifinals to Ivan Dodig and Marcelo Melo. Roger-Vasselin teamed up with Julien Benneteau, but lost in the first round to Milos Raonic and Nenad Zimonjić.
Steve Johnson and Sam Querrey were the defending champions, but lost in the quarterfinals to Juan Sebastián Cabal and Robert Farah.
Jamie Murray and Bruno Soares were the defending champions, but they chose not to participate together this year. Murray played alongside Neal Skupski, but lost in the semifinals to Ivan Dodig and Filip Polášek. Soares played alongside Mate Pavić, but lost in the semifinals to Juan Sebastián Cabal and Robert Farah.
Luke Bambridge and Jonny O'Mara were the defending champions but chose to defend their title with different partners. Bambridge played alongside Ben McLachlan, but lost in the first round to Wesley Koolhof and Fabrice Martin. O'Mara teamed up with Ken Skupski, but lost in the first round to Mate Pavić and Bruno Soares.
Dominic Inglot and Franko Škugor were the defending champions, but Inglot decided to compete in Vienna instead. Škugor played alongside Nikola Mektić, but they lost to Jean-Julien Rojer and Horia Tecău in the first round.
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.
Nicolas Mahut and Pierre-Hugues Herbert defeated Alexander Bublik and Andrey Golubev in the final, 4–6, 7–6(7–1), 6–4, to win the men's doubles title at the 2021 French Open. It was their second French Open title and fifth major title together. They saved match points in their semifinal match against Juan Sebastián Cabal and Robert Farah. Bublik and Golubev became the first male Kazakh players to reach a major final.
