The U.S. Open draw placed defending champion Serena Williams in a first-round match against Italian veteran Francesca Schiavone, the 2010 French Open winner, and a possible fourth-round dual with rising American Sloane Stephens.
An expected run to the semifinals by Williams would mean a potential meeting with either Agnieszka Radwanska, who replaced injured Maria Sharapova as the No. 3 seed, or 2011 French champion Li Na.
Also in Williams' quarter of the draw is her sister Venus, herself owner of two Open titles but this year the only unseeded former champion in the women's field. Venus begins the tournament against Belgium's Kirsten Flipkens, a Wimbledon semifinalist this year.
With the departures of Sharapova, who withdrew late Wednesday because of a shoulder injury, and Wimbledon champion Marion Bartoli, who surprised the tennis community by retiring last week, Serena Williams and No. 2 seed Victoria Azarenka, the Australian Open champ, are expected to meet in the final for a second straight year.
Among the men, No. 2 seed Rafael Nadal could face top American John Isner in the fourth round and five-time Open champ Roger Federer in the quarterfinals. If form prevails, top seed Novak Djokovic would meet the Open's 2009 winner, Juan Martin del Potro, in the quarterfinals.
Defending champion Andy Murray, in the same half of the draw as Djokovic, likely would play No. 5 Tomas Berdych in the quarterfinals.