Top seed Karolina Pliskova became the biggest casualty of this year's US Open so far as she was dumped out in the second round by Caroline Garcia of France.
Pliskova's 6-1, 7-6 defeat further obliterated a women's field already missing six of the world's top 10 - and left American Sofia Kenin as the highest seed standing.
The 2016 finalist made a dismal start as she fell a double break behind to 26-year-old Garcia, a player who has struggled to live up to initial expectations and sunk from a career high world ranking of four to her current 50.
Pliskova produced a single winner in the opening set and fell a break down in the second before belatedly rallying, breaking back and fashioning two set points on the Garcia serve at 5-4.
But just when Garcia showed signs of the kind of wobble that has hampered her career, she hauled herself back to force a tiebreak, and swept through it in style much to her evident delight.
Garcia said: "It was very close to being a third set and if so I was ready. When I got broken in the second set I didn't do anything really bad, and I had to stay focused and aggressive."
Former Wimbledon champions Angelique Kerber and Petra Kvitova kept their hopes on track after gritty second-round wins.
Kerber, the 17th seed, is playing in her 50th grand slam at the venue where she made her breakthrough, reaching the semi-final in 2011.
The 2016 Flushing Meadows winner came through a tight all-German clash against Anna-Lena Friedsam 6-4, 7-6.
Kerber, 32, who won Wimbledon two years ago, said: "It's always special to return to a place where you won. It's a really special place for me, where it all started in 2011, and I'm still here competing. This is what I love."
Kvitova, the two-time champion at SW19, has never made it further than the quarter-finals in New York.
The 30-year-old Czech, seeded six at this year's championship, was slow to get moving but eventually beat Ukrainian Kateryna Kozlova 7-6, 6-2.
She said: "It was very difficult especially with my nerves, I felt very tight. But it's a grand slam, at the beginning of the tournament it's always like this."
Varvara Gracheva produced one of the most stunning comebacks in grand slam history when she came back from 6-1, 5-1 down to beat 30th seed Kristina Mladenovic.
The 20-year-old from Russia, playing at her first major championship, saved four match points before taking the second set on a tiebreak.
France's Mladenovic promptly crumbled as Gracheva completed a remarkable 1-6, 7-6, 6-0 victory.
Afterwards Mladenovic blasted that she felt like a "prisoner" during the tournament, in which she was one of the players placed within a so-called 'bubble within a bubble', having had contact with compatriot Benoit Paire who subsequently tested positive for Covid-19.
She said: "I was playing well but I was feeling on edge. What they are forcing us to go through is abominable. I want my freedom back. I feel like we are prisoners here."