Australian Open finalists Novak Djokovic and Dominic Thiem are on a collision course to meet again in the US Open final after they were placed at opposite ends of the draw on Thursday.
World number one and top seed Djokovic clinched the year's first Grand Slam when he beat Austrian Thiem in five sets and the Serbian is unbeaten with a 21-0 record in a season upended by the COVID-19 pandemic.
With five-times winner Roger Federer and defending champion Rafa Nadal skipping the tournament due to injury and COVID-19 concerns respectively, Thiem was named the second seed.
Djokovic opens his campaign for an 18th Grand Slam victory and fourth title at Flushing Meadows against Bosnia's Damir Dzumhur while Thiem plays Spaniard Jaume Munar.
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Last year's runner-up Daniil Medvedev is seeded third and Stefanos Tsitsipas fourth. Alexander Zverev, seeded fifth, has a potentially tough first-round match against big-serving Kevin Anderson who reached the final in 2017.
Wildcard Andy Murray, playing in his first Grand Slam since undergoing hip surgery after last year's Australian Open, has a first-round clash with Japan's Yoshihito Nishioka.
With six of the women's top 10 skipping the tournament in New York, the Czech Republic's Karolina Pliskova is top seed and she begins her quest for her first Grand Slam title against Ukraine's Anhelina Kalinina.
Australian Open champion Sofia Kenin is seeded second and she faces Belgium's Yanina Wickmayer.
Serena Williams, looking to clinch a record-equalling 24th Grand Slam, is the third seed and she meets compatriot Kristie Ahn. Serena's unseeded sister Venus, playing in her 22nd US Open at the age of 40, takes on 20th seed Karolina Muchova.
Former champion Naomi Osaka plays fellow Japanese Misaki Doi while wildcard Kim Clijsters, who made a second comeback from retirement this year, plays 21st seed Ekaterina Alexandrova.