Justine Henin was the defending champion, but retired from the sport on May 14, 2008.
Serena Williams defeated Jelena Janković 6–4, 7–5 in the final, winning her third US Open title. As a result, Williams returned to World No. 1 in the WTA rankings for the first time since 2003.
Notably this was the final Grand Slam in which 1998 champion and former World No. 1 Lindsay Davenport competed in the singles championship. She lost to Marion Bartoli in the third round.