2021 US Open – Mixed doubles

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.

Arévalo became the first player from Central America to reach a Grand Slam final.

Bethanie Mattek-Sands and Jamie Murray were the two-time defending champions, having won the most recent editions in 2018 and 2019, but lost in the first round to Andreja Klepač and Joran Vliegen.

Seeds
• # 🇺🇸 Nicole Melichar-Martinez / Ivan Dodig (second round)

• # 🇺🇸 Desirae Krawczyk / 🇬🇧 Joe Salisbury (champions)

• # Alexa Guarachi / 🇬🇧 Neal Skupski (quarterfinals)

• # 🇧🇷 Luisa Stefani / 🇧🇷 Marcelo Melo (first round)

• # 🇺🇸 Bethanie Mattek-Sands / 🇬🇧 Jamie Murray (first round)

• # 🇯🇵 Ena Shibahara / 🇯🇵 Ben McLachlan (second round)

• # Chan Hao-ching / 🇳🇿 Michael Venus (first round)

• # Demi Schuurs / 🇧🇪 Sander Gillé (quarterfinals)

Wild cards
• 🇺🇸 Reese Brantmeier / 🇺🇸 Nicholas Monroe

• 🇺🇸 Elvina Kalieva / 🇺🇸 Bruno Kuzuhara

• 🇺🇸 Madison Keys / 🇺🇸 Bjorn Fratangelo

• 🇺🇸 Jamie Loeb / 🇺🇸 Mitchell Krueger

• 🇮🇳 Sania Mirza / 🇺🇸 Rajeev Ram

• 🇺🇸 Asia Muhammad / 🇺🇸 Jackson Withrow

• 🇺🇸 Sabrina Santamaria / 🇺🇸 Nathaniel Lammons

• 🇺🇸 Sachia Vickery / 🇺🇸 Nathan Pasha

Protected ranking
• 🇰🇿 Yaroslava Shvedova / 🇫🇷 Fabrice Martin

• 🇰🇿 Galina Voskoboeva / 🇷🇸 Nikola Ćaćić

Alternates
• 🇺🇸 Hayley Carter / 🇺🇸 Hunter Reese

• 🇦🇺 Ellen Perez / 🇧🇷 Marcelo Demoliner

• 🇺🇦 Dayana Yastremska / 🇦🇺 Max Purcell

Withdrawals

 * 🇨🇿 Květa Peschke / 🇩🇪 Kevin Krawietz → replaced by 🇺🇦 Dayana Yastremska / 🇦🇺 Max Purcell
 * 🇰🇿 Elena Rybakina / 🇰🇿 Andrey Golubev → replaced by 🇦🇺 Ellen Perez / 🇧🇷 Marcelo Demoliner
 * 🇷🇺 Vera Zvonareva / 🇩🇪 Tim Pütz → replaced by 🇺🇸 Hayley Carter / 🇺🇸 Hunter Reese