Top seed Karolina Pliskova was knocked out of the US Open in the second round with a heavy defeat by France's Caroline Garcia.
Unseeded Garcia recorded a 6-1, 7-6 victory to reach the third round. The wait goes on for that first Grand Slam title for Pliskova.
Czech world number three Pliskova was the highest ranked player here in the absence of Australian Ashleigh Barty and Romania's Simona Halep.
Naomi Osaka defeated Italian Camila Giorgi in straight sets to secure a third round match against Ukranian Marta Kostyuk.
Elsewhere, Angelique Kerber went past fellow German Anna-Lena Friedsam 6-3, 7-6.
The men's division saw a champion's display from four-time winner Novak Djokovic as he bounced back from a set down to beat the unseeded British hope Kyle Edmund at the Arthur Ashe Stadium.
It wasn't the Serb’s best performance but a battling one nonetheless - and he beats Edmund who started brightly but was no match for his opponent's fitness and consistent hitting.
Up next for Djokovic is German Jan-Lennard Struff, who he beat only last week.
World number 4 Stefanos Tsitsipas made the third round of the US Open for the first time after beating American Maxime Cressy 7-6, 6-3, 6-4. The Greek faces a tough test in Borna Coric next.
Fifth seed Alex Zverev survived a scare against talented teenager Brandon Nakashima but made it through to the third round of the US Open with a 7-5, 6-7, 6-3, 6-1 victory.
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