Defending champion Naomi Osaka could meet second seed Aryna Sabalenka in a US Open semi-final while top-ranked Ashleigh Barty might have a Wimbledon final rematch with Karolina Pliskova under a women's draw revealed on Thursday.
Osaka, the reigning US and Australian Open champion, was seeded third and could play Germany's Angelique Kerber in the fourth round before a possible quarter-final against Ukraine sixth seed Elina Svitolina.
The Japanese star, who pulled out of the French Open and skipped Wimbledon citing mental health issues, might then meet Belarus' Sabalenka, a semi-finalist last month at Wimbledon, or Czech eighth seed Barbora Krejcikova, this year's French Open winner.
The opposite half of the draw features top seed Barty, coming off a second Grand Slam title at Wimbledon in July, facing a possible quarter-final against Polish seventh seed Iga Swiatek.
If Barty reached the final four, she could see Czech fourth seed Pliskova in a rematch of the Wimbledon final or Canadian sixth seed Bianca Andreescu, the 2019 US Open champion who skipped last year's New York hardcourt showdown.
Serena Williams, a 23-time Grand Slam champion, and her sister Venus, a seven-time Grand Slam winner, withdrew from the event on Wednesday due to injuries.
Osaka, a two-time US and Australian Open champion, opens against Czech Marie Bouzkova and could meet American Alycia Parks or a qualifier in round two.
In the fourth round, Osaka could meet Kerber but that section of the draw also includes US 21st seed Coco Gauff, whose potential second-round foe would be the winner between compatriots Sloane Stephens and Madison Keys in a rematch of the 2017 US Open final won by Stephens.
Svitoina's path to the last eight opens against a qualifier and could feature a fourth-round encounter with Romania's Simona Halep, a former world number one who won the 2018 French Open and 2019 Wimbledon crowns.
Sabalenka's quarter of the draw includes Krejcikova and two-time Grand Slam champions Garbine Muguruza of Spain and Victoria Azarenka of Belarus, the 2020 US Open runner-up.
Barty opens against Russia's Vera Zvonareva, a 2010 US Open runner-up, and could meet US 13th seed Jen Brady in the round of 16.
Pliskova and Andreescu are the top seeds in their quarter of the draw. The highest-ranked obstacle to Pliskova's place in the last eight is Russian number 14 Anastasia Pavlyuchenkova while Andreescu has 10th-ranked Czech Petra Kvitova, a two-time Wimbledon champion, in her section of the draw.