(CNN) -- World number one Rafael Nadal faces Russian Teymuraz Gabashvili in the first round as he bids to become the seventh man to win all four grand slam events at next week's U.S. Open.
The hard court grand slam is the only one to elude the Spanish ace and if he gets past Gabashvili either Argentina's Maximo Gonzalez or Uzbek Denis Istomin awaits in the second round.
A possible semifinal opponent for Nadal could be world number four Andy Murray, who won their last clash in Toronto earlier this month.
But Nadal beat the Scot in the semifinals as he reclaimed his Wimbledon crown this year and took over as world number one from Federer, who has been in the past six finals at Flushing Meadows.
Federer, who won the Cincinnati Masters at the weekend, opens against Argentina's Brian Dabul.
He could face Robin Soderling of Sweden in the quarters and world number three Novak Djokovic in the last four.
Argentina's Juan Martin Del Potro is unable to defend the title he won by beating Federer in the final due to injury.
Murray, who is bidding for his first grand slam title, will begin his campaign against Slovakia's Lukas Lacko, while Djokovic opens against Serbian compatriot Viktor Troicki.
Kim Clijsters, who has been battling a thigh injury, has been drawn against Hungary's Greta Arne as she begins the defense of the title she won in such dramatic fashion last year.
World number one Serena Williams is sidelined through injury with Dane Caroline Wozniacki installed as top seed. She opens against Chelsey Gullickson of the United States.
Third seed Venus Williams has been drawn to play Roberta Vinci of Italy in her first match in New York.