The Williams sisters were eliminated by the Czech pair of Lucie Hradecka and Linda Noskova 7-6 (5), 6-4 at Flushing Meadows.
Sania Mirza and Lucie Hradecka produced some high-quality tennis but lost 4-6 3-6 to Coco Gauff and Jessica Pegula in the third round.
The Indo-Croatian duo of Sania Mirza and Mate Pavic defeated David Vega Hernandez and Natela Dzalamidze in the Wimbledon 2022 first round.
Sania Mirza and Lucie Hradecka had reached the final after handing a shock defeat to top seeds Zhang Shuai and Caroline Dolehide.
Sania Mirza will be in action once again in the mixed doubles partnering Mate Pavic of Croatia in the mixed doubles event.