Former champion Andy Murray will play Japan's Yoshihito Nishioka in the first round of the behind-closed-doors US Open at Flushing Meadows in New York.
The Briton, 33, is playing singles at a major for the first time since the 2019 Australian Open after injury problems.
British number one Johanna Konta plays her compatriot Heather Watson, while Kyle Edmund could face men's top seed Novak Djokovic in round two.
The Grand Slam starts on Monday - but without a host of star names.
Those missing include defending champions Rafael Nadal and Bianca Andreescu, who are not playing because of the coronavirus pandemic.
There are no qualifying rounds or mixed doubles, with the men's and women's doubles reduced to 32 teams and the wheelchair events taking place after initially being omitted by the USTA.
Who are the Britons facing?
Six British players are playing in the singles at Flushing Meadows, with 2012 champion Murray the star attraction as he continues his comeback after two major hip surgeries.
The Scotsman is now ranked 134th in the world but reached the last 16 at the Western and Southern Open this week, which was his first top-level tournament since November because of niggling injuries and the suspension of the ATP Tour.
Konta, ranked 15th, is perhaps the nation's best hope of success and has looked in fantastic form having reached the semi-finals of the same tournament.
The ninth seed must first overcome 52nd-ranked Watson, who has lost all three of their previous meetings on the WTA Tour.
British men's number one Dan Evans, 30, is seeded 23rd after reaching a career-high ranking of 28 this year and he plays 20-year-old Brazilian Thiago Seyboth Wild, who features in the main draw of a Grand Slam for the first time.
Former Australian Open semi-finalist Edmund, ranked 44th, faces Kazakhstan's Alexander Bublik and is likely to face Serbia's Djokovic in the next round - assuming the 17-time Grand Slam champion beats 107th-ranked Damir Dzumhur of Bosnia and Herzegovina.
British number three Cameron Norrie faces a tough task against Argentine ninth seed Diego Schwartzman.
What about the other big names?
The women's field, in particular, has been weakened by the withdrawals, with only four of the world's top 10 set to play.
American great Serena Williams, bidding for a record-equalling 24th Grand Slam, faces compatriot Kristie Ahn in her opener, while 16-year-old Coco Gauff takes on Latvian 31st seed Anastasija Sevastova.
Gauff could potentially play 2018 champion Naomi Osaka, who starts against fellow Japanese player Misaki Doi, in the third round for the third consecutive Grand Slam.
Osaka had to console Gauff after overwhelming her in a comfortable US Open defeat last year, before the American teenager stunned the defending champion at the Australian Open in January.
On the men's side, another notable absentee is Swiss great Roger Federer, who is recovering from knee surgery.
The absence of Nadal and Federer means Austria's Dominic Thiem is seeded second and he starts against Spain's Jaume Munar.
German fifth seed Alexander Zverev takes on 2018 Wimbledon runner-up Kevin Anderson in another notable opening-round match.
Analysis
BBC tennis correspondent Russell Fuller
So a first-round meeting between Johanna Konta and Heather Watson is assured; and there could be another British clash later in the first week.
But Andy Murray and Dan Evans have plenty of work to do before they meet in the third round, in what is likely to be a spectacularly unpredictable Grand Slam.
Murray's first-round opponent Nishioka is at a career-high world ranking of 48, and he might also have to play 20-year-old Felix Auger-Aliassime, who is already a five-time runner-up on the ATP Tour.
There could also be a third-round meeting between Naomi Osaka and Coco Gauff. If they were to meet, it would be for the third Grand Slam in a row.