Novak Djokovic launches his quest for a US Open title to complete a calendar-year Grand Slam on Tuesday when he faces Danish qualifier Holger Rune at Arthur Ashe Stadium.
World number one Djokovic would become the first man since Rod Laver in 1969 to capture all four Grand Slam titles in the same year if he captures his fourth US Open title.
The 34-year-old Serbian boosted his career Grand Slam total to 20 by taking this year's Australian and French Opens and Wimbledon titles, matching Roger Federer and Rafael Nadal for the all-time men's record.
Djokovic will face Rune in Tuesday's first night match at Arthur Ashe Stadium followed by Canadian sixth seed Bianca Andreescu opening against Swiss Viktorija Golubic.
Andreescu, the 2019 US Open winner, skipped last year's event.
Tuesday's day session at Ashe starts with Tokyo Olympic champion Alexander Zverev of Germany facing American Sam Querrey.
The second day match pits world number one Ashleigh Barty of Australia, who won last month's Wimbledon title, facing Russia's Vera Zvonareva.
Other matches of note send Czech fourth seed Karolina Pliskova against US wildcard Catherine McNally to start play at Louis Armstrong Stadium.
Japan's Kei Nishikori, the 2014 US Open runner-up, starts the Grandstand lineup against Italy's Salvatore Caruso while Italian sixth seed Matteo Berrettini meets Frenchman Jeremy Chardy next.