Liezel Huber and Bob Bryan defeated Květa Peschke and Aisam-ul-Haq Qureshi in the final, 6–4, 6–4 to win the mixed doubles tennis title at the 2010 US Open.

Carly Gullickson and Travis Parrott were the defending champions, but lost in the first round to Gisela Dulko and Pablo Cuevas.