Olympic champion Rafael Nadal begins his run at a career-first US Open title as he faces off against a qualifier after the draw made on Thursday, dpa reported.
The 22-year-old Spaniard will play his first major as a top seed after taking over from Roger Federer after the Swiss player's four- and-a-half year run at the top ended on Monday.
Nadal has won two of three Grand Slams this season, defeating Federer at Paris and Wimbledon before beating Fernando Gonzalez in the Olympic final last weekend in Beijing.
Federer is seeded an unfamiliar second, starting his bid for a consolation fifth straight New York title against Argentine Maximo Gonzalez, the number 114.
Third seed Novak Djokovic is in Federer's lower half of the draw, with a possible semi-final looming. Djokivic starts with veteran Frenchman Arnaud Clement.
Serbs lead the women's seedings, with Ana Ivanovic back on the top spot after an interlude at the summit by compatriot Jelena Jankovic.
The top seed faces Russian Vera Dushevina in the first round while Jankovic plays Californian wild-card Coco Vandeweghe.
The bottom of the women's draw is heavy with outstanding Russians. Third seed Svetlana Kuznetsova, winner of the event four years ago, could find herself in a quarter-final with compatriot and Olympic champion Elena Dementieva.