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.
Angelique Kerber has been knocked out of the US Open after losing to Dominika Cibulkova
The Slovakian proved a step too far for the Wimbledon champion, 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