Former champion Andy Murray will face Greek third seed Stefanos Tsitsipas in the first round of the US Open.
Top seed Novak Djokovic, bidding for a record 21st Grand Slam men's singles title and a clean sweep of the majors in 2021, starts against a qualifier.
Ashleigh Barty, the women's world number one, faces Vera Zvonareva, while Britain's top-ranked woman Johanna Konta plays Kristina Mladenovic.
The final Grand Slam of the season starts in New York on Monday.
Defending women's champion Naomi Osaka, who is bidding for a third title in four years, is seeded third and has been drawn in the opposite half to Australia's Barty.
The Japanese player begins her title defence against Marie Bouzkova of the Czech Republic.
Britain's Cameron Norrie, seeded 26th, opens against highly-rated Spanish teenager Carlos Alcaraz, while the nation's top-ranked male player Dan Evans faces Brazilian Thiago Monteiro.
Heather Watson - the only other British player to have gained direct entry into the main draws - plays Slovenia's Kaja Juvan.
The tournament - which is the first major since the coronavirus pandemic to be held with a 100% crowd throughout - will be without a host of star names.
American great Serena Williams, who turns 40 next month, pulled out of her home major on Wednesday with the hamstring injury which forced her to retire from her first-round match at Wimbledon.
Hours later, the six-time champion's sister Venus Williams, 41, also withdrew with a long-standing leg injury.
Swiss five-time champion Roger Federer, 40, is out following knee surgery, while long-time rival Rafael Nadal, 35, has ended his season because of a niggling foot injury.