Justine Henin-Hardenne defeated Kim Clijsters in the final, 7–5, 6–1 to win the women's singles tennis title at the 2003 US Open.

Serena Williams was the reigning champion, but did not participate due to injury.

Defending finalist Venus Williams also withdrew before the tournament due to injury, marking the first time in the Open Era that neither of the reigning US Open finalists returned.

This was also the only major between the 1997 Australian Open and the 2011 French Open (a span of 56 events) where neither of the Williams sisters competed.

This marked the first US Open main draw appearance of future champion Flavia Pennetta; she lost to Svetlana Kuznetsova in the first round.