Emma Raducanu will face fellow Grand Slam winner Sofia Kenin in the Briton's first US Open appearance for two years.
Raducanu memorably triumphed at the US Open as a teenage qualifier in 2021, becoming the first British woman for 44 years to win a major singles title.
She lost in the first round in 2022 and missed last year's tournament after having wrist and ankle surgery.
The 21-year-old faces a potentially tricky task against American Kenin, who won the Australian Open in 2020 and reached the French Open final in the same year.
Katie Boulter, the British women's number one and 31st seed, will start against an as-yet unconfirmed qualifier, while Harriet Dart faces Chloe Paquet of France.
In the men's draw, Jack Draper faces China's Zhang Zhizhen, with Carlos Alcaraz potentially waiting in the third round.
Dan Evans, the only other British man to gain direct entry into the main draw, faces 23rd seed Karen Khachanov of Russia.
Jan Choinski reached the main draw for the first time with a hard-fought 6-0 6-7 (5-7) 7-6 (12-10) win over American Maxime Cressy.
However, three other Britons - Sonay Kartal, Lily Miyazaki and Billy Harris - all lost in the final round of qualifying.
The US Open takes place from 26 August to 8 September.