There will be four different grand slam champions for the second successive season after Wimbledon winner Angelique Kerber joined Simona Halep and Caroline Wozniacki in making an early exit in New York.
Kerber was the last women to collect two slam titles in a season, winning the Australian and US Opens in 2016 before a dramatic slump last year.
She has been resurgent under Wim Fissette, capped by her brilliant victory over Serena Williams at Wimbledon, and had reached at least the quarter-finals at all of the slams, but here she found Dominika Cibulkova a step too far, the Slovakian winning 3-6 6-3 6-3.
Kerber said: “I had my chances, but I couldn’t take them, especially in the third set. Also, I was not able actually to play my best tennis in the important moments.
“She was going for it, and she hit the balls really good and played the winners when she has to. I think that was the difference about the match today. You have sometimes days where you are trying everything, but it’s not really working as you wish.”
The defeats for Kerber, Halep and Wozniacki – all on the new Louis Armstrong Stadium – mean defending champion Sloane Stephens is the only one of the top four seeds still left in the tournament.
The sixth seed also went on Saturday, with Caroline Garcia beaten 5-7 6-4 7-6 (7/4) by Carla Suarez Navarro.
Cibulkova next plays last year’s runner-up, Madison Keys, who avoided an upset by fighting from a set down to defeat Aleksandra Krunic 4-6 6-1 6-2.
Serbian Krunic had a dreadful build-up to the tournament, winning just four games in three matches, but has hit form again in New York and played an excellent first set before Keys turned it around.
Another upset saw Cincinnati champion Kiki Bertens beaten 7-6 (7/4) 2-6 7-6 (7/1) by Czech teen Marketa Vondrousova.
Bertens, a quarter-finalist at Wimbledon, made herself a dark horse for the title by defeating Halep to win her biggest WTA Tour crown two weeks ago but admitted to feeling mentally and physically tired.
She said: “It was tough for me to keep calm today, to keep my focus all the time, to just stay relaxed, to just play the points and not complain about anything. That was, I think, the key today.”
Vondrousova next faces Ukraine’s Lesia Tsurenko, who followed up her victory over Wozniacki by beating Katerina Siniakova 6-4 6-0.
Naomi Osaka has been the most efficient player over the first three rounds and the 20-year-old Japanese-American blasted her way into the last 16 of grand slam for only the second time with a 6-0 6-0 victory over Aliaksandra Sasnovich.
Osaka’s last two matches have lasted just 50 minutes each and she has only lost seven games in three rounds.