Bradley Klahn and Jackson Withrow were the defending champions but only Klahn chose to defend his title, partnering Robert Galloway. Klahn successfully defended his title.
Marcelo Arévalo and Miguel Ángel Reyes-Varela were the defending champions but only Arévalo chose to defend his title, partnering Roberto Maytín. Arévalo lost in the first round to Luis David Martínez and David Pérez Sanz.
Brydan Klein and Joe Salisbury were the defending champions but chose not to defend their title.
Leander Paes and Purav Raja were the defending champions but only Paes chose to defend his title, partnering Miguel Ángel Reyes-Varela. Paes lost in the quarterfinals to Alex Lawson and Jackson Withrow.
Jeevan Nedunchezhiyan and Christopher Rungkat were the defending champions but chose not to defend their title.
Marc-Andrea Hüsler and Sem Verbeek were the defending champions but chose not to defend their title.
Robert Galloway and Roberto Maytín were the defending champions but only Maytín chose to defend his title, partnering Jackson Withrow. Maytín lost in the final to Diego Hidalgo and Martin Redlicki.
Evan King and Hunter Reese were the defending champions but chose not to defend their title.
Hans Hach Verdugo and Luke Saville were the defending champions but only Hach Verdugo chose to defend his title, partnering Dennis Novikov. Hach Verdugo lost in the first round to Alex Lawson and Jackson Withrow.
Sanchai Ratiwatana and Christopher Rungkat were the defending champions but chose not to defend their title.
Harri Heliövaara and Henri Laaksonen were the defending champions but chose not to defend their title.
Robert Galloway and Nathaniel Lammons were the defending champions but only Lammons chose to defend his title, partnering Hunter Reese. Lammons lost in the first round to Sekou Bangoura and Sebastian Korda.
JC Aragone and Marcos Giron were the defending champions but lost in the first round to Gong Maoxin and Hunter Reese.
Romain Arneodo and Andrei Vasilevski were the defending champions but chose not to defend their title.
Grégoire Barrère and Albano Olivetti were the defending champions but lost in the first round to Ruben Bemelmans and Daniel Masur.
Rajeev Ram and Joe Salisbury defeated defending champion Bruno Soares and his partner, Jamie Murray, in the final, 3–6, 6–2, 6–2, to win the men's doubles tennis title at the 2021 US Open. This was the second major title for Ram and Salisbury as a team after they first won the 2020 Australian Open together. Ram and Salisbury saved four match points in their quarterfinal match against Matthew Ebden and Max Purcell en route to the title.
Desirae Krawczyk and Joe Salisbury defeated Giuliana Olmos and Marcelo Arévalo in the final, 7–5, 6–2 to win the mixed doubles tennis title at the 2021 US Open. By winning the title, Krawczyk and Salisbury received their third and second major mixed doubles title, respectively. Their victory together made Krawczyk the first player to win three consecutive mixed doubles major trophies since Mahesh Bhupathi in 2005 and 2006, and the seventh player in the Open Era to win three mixed doubles titles in a single season. Salisbury became the first man to win both the men's doubles and mixed doubles titles at the US Open in the same year since Bob Bryan in 2010.
Ruben Bemelmans and Daniel Masur were the defending champions but lost in the first round to Marc-Andrea Hüsler and Dominic Stricker.
Nathaniel Lammons and Jackson Withrow were the defending champions but only Withrow chose to defend his title, partnering Denys Molchanov. Withrow lost in the quarterfinals to Andrej Martin and Tristan-Samuel Weissborn.
Marcelo Arévalo and Jean-Julien Rojer defeated Ivan Dodig and Austin Krajicek in the final, 6–7(4–7), 7–6(7–5), 6–3 to win the men's doubles tennis title at the 2022 French Open. They saved three championship points en route to winning their first major title as a team and their third overall title together. With his maiden major title, Arévalo became the first men's doubles major champion from Central America, and at 40 years of age, Rojer became the oldest men's doubles major champion in the Open Era with his third major men's doubles title.
JC Aragone 
Darian King 
