Defending men's champion Novak Djokovic will kick off his title defence against Roberto Carballes Baena, and last year's women's champion, Naomi Osaka, will face Anna Blinkova.
Roger Federer will go up against a qualifier, and Rafael Nadal will take on John Millman in the opening round. Coco Gauff, the 15-year-old Wimbledon standout, will face Anastasia Potapova, while Simona Halep will battle a qualifier.
The top story to emerge from the draw is the clash between Williams and Sharapova, however. It will mark their first meeting in Flushing Meadows and has tennis writer Jose Morgado excited:
SB Nation profiled the rivalry, which saw its first major showdown when Sharapova beat Williams during the 2004 Wimbledon final at age 17.
Per ABC, excerpts from the Russian's biography, Unstoppable, which detailed that encounter and the aftermath, did not sit well with the 37-year-old, who called the book "disappointing."
On the court, the rivalry has been one-sided:
Sharapova won the last meeting between the two, but that was a walkover during the 2018 French Open. The 32-year-old hasn't beaten Williams on the court since 2004 at the WTA Championships.
Williams is a six-time champion at Flushing Meadows, while Sharapova has won a single title in New York, in 2006.