Andy Murray has been drawn against Francisco Cerundolo in the first round of the US Open.
The Scottish former world number 1, who won the New York tournament in 2012 and was defeated in the 2008 final, will play the Argentine 24th seed when in the Grand Slam tournament that kicks off at Flushing Meadows on Monday.
Current British number 1 Cameron Norrie will play unpredictable Frenchman Benoit Paire.
Norrie is seeded in the top eight for the first time at a grand slam at seven, in the absence of Novak Djokovic who accepted on Thursday that he will not be able to play in the tournament because of his unvaccinated status.
Emma Raducanu will begin the defence of her US Open title against French veteran Alize Cornet.
The 19-year-old returns as the 11th seed 12 months after her incredible triumph but will be wary of Cornet, who ended Iga Swiatek’s 37-match unbeaten run at Wimbledon and has had a number of other big grand slam wins.
Serena Williams begins what seems set to be her final tournament against Montenegro’s Danka Kovinic and could face second seed Anett Kontaveit in round two.
Kyle Edmund, playing singles at a grand slam for the first time in two years following three knee operations, has been handed a very tough opener against fifth seed Casper Ruud.
In a mixed draw for the British players, debutant Jack Draper, who is chasing a first ATP Tour title in Winston-Salem this week, will take on Finn Emil Ruusuvuori, 20th seed Dan Evans faces Czech Jiri Vesely and Harriet Dart meets 10th seed Daria Kasatkina.
The most eye-catching first-round matches pit two-time former champion Naomi Osaka against Australian Open finalist Danielle Collins – with the winner potentially to face Raducanu in round three – while Nick Kyrgios faces his close friend and doubles partner Thanasi Kokkinakis.
Defending champion Daniil Medvedev is the top seed after Djokovic admitted defeat in his bid for entry and the Russian begins his campaign against American Stefan Kozlov.
Djokovic, who has won three times at Flushing Meadows among his 21 total grand slams, was hoping the United States would change its long-standing rules to allow non-citizens without a coronavirus vaccine to enter the country.
The Wimbledon champion, who was also banned from playing in the Australian Open due to his anti-vaccination stance, said after his SW19 success in July that he was waiting “hopefully for some good news from USA”.
But he tweeted on Thursday: “Sadly, I will not be able to travel to NY this time for US Open. Thank you #NoleFam for your messages of love and support.
“Good luck to my fellow players! I’ll keep in good shape and positive spirit and wait for an opportunity to compete again. See you soon tennis world!”
A statement from tournament director Stacey Allaster read: “Novak is a great champion and it is very unfortunate that he will be unable to compete at the 2022 US Open, as he is unable to enter the country due to the federal government’s vaccination policy for non-U.S. citizens. We look forward to welcoming Novak back at the 2023 US Open.”
Second seed Rafael Nadal, back at Flushing Meadows for the first time since winning his fourth title in New York three years ago, faces Australian Rinky Hijikata while women’s number one seed Swiatek opens against Jasmine Paolini of Italy.