Carlos Alcaraz will begin his bid for a third straight grand slam success against a qualifier at the US Open, while top seed Jannik Sinner will face Mackenzie McDonald in the first round.
Alcaraz won his fourth major title at Wimbledon in July, dominating Novak Djokovic in the final after also triumphing at the 2022 US Open, Wimbledon in 2023 and the French Open earlier this year.
Should the Spaniard progress through his first-round match, he could take on Botic van de Zandschulp in round two and Britain's Jack Draper in the third round.
Seeded third, Alcaraz could face world number one Sinner in the semi-finals, with the Italian starting his campaign against a home favourite in McDonald.
Sinner recently avoided a ban after twice testing positive for banned substance clostebol, with an independent tribunal finding he was inadvertently given the steroid in an over-the-counter spray by his physiotherapist Giacomo Naldi.
On the other side of the men's draw, Djokovic will also start against a qualifier as he bids to finally surpass Margaret Court's overall record of 24 grand slam titles.
Djokovic won his 24th major crown at the 2023 tournament at Flushing Meadows, beating Daniil Medvedev in straight sets in the final.
He has struggled to find top gear at this year's grand slams, though he did claim his first Olympic gold medal by beating Alcaraz in the showpiece match at Roland-Garros.
In the women's draw, top seed Iga Swiatek will start against a qualifier while Coco Gauff will open her title defence by taking on Varvara Gracheva, with a testing third-round date with Elina Svitolina potentially on the cards for the third-seeded American.
Aryna Sabalenka joins Swiatek in facing a qualifier first, while there is a tricky draw for 2021 US Open winner Emma Raducanu, who is set for her first Flushing Meadows appearance since 2022.
She will take on the United States' 2020 Australian Open winner Sofia Kenin, with the victor set to face another American in round two, in either Shelby Rogers or sixth seed Jessica Pegula.
The first round of the US Open begins on Monday, with the women's singles final set for September 7 and the men's showpiece match taking place one day later.