Brydan Klein and Dane Propoggia are the defending champions but chose to defend their title with different partners. Klein partnered Bradley Mousley and lost in the semifinals to Gerard and Marcel Granollers. Propoggia partnered Vijay Sundar Prashanth but lost in the first round to Andrew Harris and Luke Saville.
Bradley Mousley and Luke Saville were the defending champions but chose to defend their title with different partners. Mousley partnered Alex Bolt and successfully defended his title. Saville partnered Matt Reid but lost in the quarterfinals to Max Purcell and Andrew Whittington.
Scott Lipsky and Leander Paes were the defending champions but chose not to defend their title.
Peter Polansky and Neal Skupski were the defending champions but chose not to defend their title.
Alex Bolt and Max Purcell were the defending champions but only Purcell chose to defend his title, partnering Lloyd Harris. Purcell lost in the semifinals to Joris De Loore and Marc Polmans.
James Cerretani and Neal Skupski were the defending champions but only Skupski chose to defend his title, partnering Luke Bambridge. Skupski successfully defended his title.
Alex Bolt and Bradley Mousley were the defending champions but only Mousley chose to defend his title, partnering Akira Santillan. Mousley lost in the first round to Adam and Jason Taylor.
Alex Bolt and Bradley Mousley were the defending champions but only Mousley chose to defend his title, partnering Akira Santillan. Mousley lost in the quarterfinals to Evan Hoyt and Wu Tung-lin.
Jay Clarke was the defending champion but chose not to defend his title.
Gong Maoxin and Zhang Ze were the defending champions but chose not to defend their title.
Hsieh Cheng-peng and Yang Tsung-hua were the defending tennis champions and successfully defended their title, defeating Evan King and Hunter Reese 6–4, 7–6(7–4) in the final.
Jeremy Beale and Marc Polmans were the defending champions but only Polmans chose to defend his title, partnering Evan King. Polmans lost in the first round to Marcelo Tomás Barrios Vera and Alejandro Tabilo.
Evan King and Nathan Pasha were the defending champions but chose to defend their title with different partners. King partnered Fernando Romboli but lost in the first round to Robert Galloway and Hans Hach Verdugo. Pasha partnered Max Schnur but lost in the first round to Carlos Gómez-Herrera and Viktor Troicki.
Rajeev Ram and Joe Salisbury defeated the 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. It was the second major title for Ram and Salisbury as a team, following the 2020 Australian Open. Ram and Salisbury saved four match points en route to the title, in the quarterfinals against Matthew Ebden and Max Purcell.
Guido Andreozzi and Andrés Molteni were the defending champions but only Andreozzi chose to defend his title, partnering Thiago Seyboth Wild. Andreozzi withdrew from the tournament before his quarterfinal match.
Ariel Behar and Gonzalo Escobar were the defending champions but chose not to defend their title.
Max Purcell and Luke Saville were the defending champions but only Purcell chose to defend his title, partnering Marc Polmans. Purcell withdrew before his semifinal match against Chung Yun-seong and Aleksandar Kovacevic due to injury.
Gijs Brouwer and Reese Stalder were the defending champions but only Stalder chose to defend his title, partnering Evan King. Stalder lost in the first round to André Göransson and Ben McLachlan.
Kaichi Uchida and Wu Tung-lin were the defending champions but chose not to defend their title.
Nicolás Barrientos and Miguel Ángel Reyes-Varela were the defending champions but chose not to defend their title.
Evan King 
Max Purcell 
Rubin Statham 
