Defending champion Kim Clijsters defeated Vera Zvonareva in the final, 6–2, 6–1 to win the women's singles tennis title at the 2010 US Open.

It was her third non-consecutive US Open title, having won on her last two appearances in 2005 and 2009 (she did not play in 2006 due to injury, and was retired from the sport in 2007 and 2008).

1 and three-time champion Serena Williams withdrew from the tournament due to a foot surgery sustained from an exhibition match.

Caroline Wozniacki was in contention to gain the top ranking by winning the title, but lost to Zvonareva in the semifinals.

3 and Olympic gold medalist Elena Dementieva; she was defeated in the fourth round by Samantha Stosur.