Angelique Kerber and Petra Kvitova were both knocked out of the US Open on Saturday, leaving defending champion Sloane Stephens as the sole remaining top-six seed in the women’s draw.
Wimbledon champion Kerber was beaten 3-6 6-3 6-3 by Slovak 29th seed Dominika Cibulkova in the third round.
Two-time quarter-finalist Kvitova lost 7-5 6-1 to in-form Belarusian Aryna Sabalenka.
None of this year’s Grand Slam winners are now left in the women’s singles.
French Open champion Simona Halep was knocked out by Kaia Kanepi in the first round, while Australian Open champion Caroline Wozniacki experienced a shock second-round loss to Ukraine’s Lesia Tsurenko.
- Sharapova beats Ostapenko to reach fourth round
- Live scores, schedules and results
- Alerts: Get tennis news sent to your phone
Kerber broke three times in the first set but Cibulkova repeated the feat in the second to take it to a decider.
The German fourth seed, 30, was then broken again twice in the final set and misses out on a last-16 tie with last year’s finalist Madison Keys.
American 14th seed Keys, runner-up to Stephens last year, recovered from a set down to reach the last 16, beating Serbia’s Aleksandra Krunic 4-6 6-1 6-2.
Keys, 23, was broken in her first service game of the match en route to losing the first set but broke twice in the second set to take it to a decider.
The first five games of the third set went against serve before the American held for 4-2 and closed out the match.
“I was definitely a little bit nervous and she came out playing really well and put pressure on me from the start. I am just happy to be in the next round,” Keys, 23, said.
“There were too many unforced errors in the first set but I’m glad I settled down a bit and played much better. I wasn’t aggressive enough in the first set and was too passive. The biggest thing was trusting myself.”
Battle of the 20-year-olds in the fourth round
Sabalenka warmed up for Flushing Meadows with a first career title at New Haven and came into the tournament at a career-high world ranking of 20th.
The 26th seed hit 21 winners to defeat Czech fifth seed Kvitova, 28, and will face fellow 20-year-old Naomi Osaka, for a quarter-final spot after the Japanese 20th seed thrashed Belarusian Aliaksandra Sasnovich 6-0 6-0.
“I really like to play on the big stages,” Sabalenka said. “I really like to feel the support of the people. I didn’t expect anything, I just went on the court and tried for every point and now I’m so happy.”
Kvitova’s exit also means just three of the top 10 women’s seeds made it into the fourth round, with Ukraine’s Elina Svitolina (seeded seventh) and Czech Karolina Pliskova, the eighth seed, both through.
Another high-ranked departure was French sixth seed Caroline Garcia, conqueror of Britain’s Johanna Konta in round one, who lost 5-7 6-4 7-6 (7-4) to Carla Suarez-Navarro.
After taking the first set, Garcia was broken in the opening game of the second set and could not find a way back, before losing a tight third set on a tie-break.
Spanish 30th seed Suarez-Navarro will face Russian former champion Maria Sharapova after she beat Latvian 10th seed Jelena Ostapenko 6-3 6-2.
Elsewhere, Dutch 13th seed Kiki Bertens was knocked out by Czech Marketa Vondrousova 7-6 (7-4) 2-6 7-6 (7-1).