Reigning US Open women's champion Iga Swiatek saw the defence of her crown come to an end as she lost in three sets to 20th seed Jelena Ostapenko in the fourth round.
The world number one had not dropped a set en route to the last 16 and was on course to continue that hot streak at Arthur Ashe Stadium, but Ostapenko produced a terrific comeback to prevail 3-6 6-3 6-1 in one hour and 48 minutes.
A ruthless start to her latest Flushing Meadows run had seen Swiatek inflict bagels on Rebecca Peterson and Kaja Juvan in two of her first three matches, although she was hit with a harsh wake-up call as Ostapenko broke in the opening game of Sunday's affair.
The Latvian lost her serve immediately, though, and Swiatek refused to relinquish a 5-2 lead in the dying embers of the first set, but an inspired Ostapenko came out all guns blazing after dropping the opener.
The 2017 French Open champion won the first three games of the second set before levelling the contest and left Swiatek dumbfounded by racing into a 5-0 lead in the decider, although the Pole did earn one break back in the sixth game.
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However, while serving to stay in the contest, Swiatek was undone by Ostapenko's ferocious forehand, as the Latvian found the corner with her 31st winner of the day to reach the quarter-finals for the very first time.
Ostapenko will battle for a place in the final four against home favourite Coco Gauff, who was pushed all the way by the returning Caroline Wozniacki but eventually came through 6-3 3-6 6-1.
Despite hitting 44 unforced errors throughout the contest, Gauff responded in kind with 33 winners compared to just 14 for Wozniacki, who was competing in her first Grand Slam since the 2020 Australian Open.
The American teenager immediately went a break down in the deciding set, but she roared back with a six-game winning streak to advance to the last eight and continue her quest for a first major honour.
Meanwhile, Romanian 30th seed Sorana Cirstea followed up her third-round win over Elena Rybakina with another statement victory over Belinda Bencic, triumphing 6-3 6-3 in 85 minutes.
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In what will be her first Grand Slam quarter-final appearance since the 2009 French Open, Cirstea will pit her wits against Karolina Muchova, who overcame China's Wang Xinyu 6-3 5-7 6-1.
In the men's singles, Novak Djokovic drew level with Roger Federer on 26 hard-court Grand Slam fourth-round victories with a straightforward 6-2 7-5 6-4 win over Croatian qualifier Borna Gojo.
Gojo did break Djokovic's serve at the start of the second set, but the Serbian recovered with an incredibly composed display, hitting a mere 12 unforced errors compared to Gojo's 40.
The American crowd also celebrated three of their own reaching the men's singles quarter-finals, as Taylor Fritz set up a clash with Djokovic thanks to a 7-6[2] 6-4 6-4 beating of Dominic Stricker.
Frances Tiafoe also strolled past Rinky Hijikata 6-4 6-1 6-4, and he will meet Ben Shelton in an all-American last eight after the 20-year-old defeated compatriot Tommy Paul 6-4 6-3 4-6 6-4.
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