Veteran stars Serena Williams, a six-time US Open champion, and Maria Sharapova, the 2006 champion, will face off in the opening round at Flushing Meadows next week.
It will be their first meeting at Flushing Meadows, where Williams, 37, won her first grand slam title 20 years ago.
Williams, seeded eighth, has won 23 grand slam titles – the last at the Australian Open in 2017.
That compares with five for Sharapova, 32, whose last grand slam win was at the 2014 French Open.
Williams holds a 19-2 record over Sharapova, who last year reached the round of 16 at the US Open.
Sharapova defeated Williams in their last meeting, a round-of-16 pairing at the 2018 French Open.
Thursday’s draw for the final grand slam of the year also set the opening-round match for top women’s seed and defending champion Naomi Osaka.
She will face Anna Blinkova of Russia, ranked 93rd.
Osaka, 21, defeated Williams in a heated women’s singles final last year that saw the American penalised after arguing with the chair umpire over penalties for coaching and racquet abuse and and Osaka shedding tears during the award ceremony.
The Japanese went on to win the 2019 Australian Open.
Second seed Ashleigh Barty, this year’s French Open champion, will face Kazakh Zarina Diyas in the first round of the US Open.
It will be the first time the 23-year-old Australian, who won three of her six career titles this year, faces the 77th-ranked 25-year-old from Kazakhstan.
Wimbledon champion and Simona Halep, who will be seeking her first US Open crown, faces a qualifier.
The Romanian fourth seed will be seeking her third career grand slam trophy.
Karolina Pliskova of the Czech Republic, seeded third, faces a qualifier in the first round.