World number one Roger Federer was drawn on Wednesday to begin the defence of his US Open title against Wang Yeu-Tzuoo of Taipei.
The Swiss, who won his eighth Grand Slam title at Wimbledon last month, is bidding to become only the third man, after John McEnroe and Ivan Lendl, to win three consecutive titles at Flushing Meadows.
Second seed and French Open champion Rafael Nadal will meet former US Open runner-up Mark Philippoussis of Australia in his first match.
Twice former champion Andre Agassi, who will retire after the tournament, was drawn to play Romanian Andrei Pavel.
Women's world number one Amelie Mauresmo, who won the Australian Open and Wimbledon titles this year, will take on a qualifier in her opening match.
The US Open will be held from Aug 28 to Sept 10.