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Third-seeded Andy Murray was knocked out of the US Open by big-serving South African Kevin Anderson, who reached his first grand slam quarter-final with a 7-6(5), 6-3, 6-7(2), 7-6(0) win on Monday.
Murray had battled his way back from two sets down in the second round against France's Adrian Mannarino, but could not work another miracle against the 14th-ranked, 29-year-old Anderson, who swept the final tiebreak 7-0.
Anderson, the 15th seed who had lost the seven previous times he had reached the Round of 16 in a grand slam, broke through with a brilliant display of serving in the final tiebreak.
He cracked his 25th ace along with two other service winners in ending the match, the longest of the tournament, after four hours and 18 minutes.
"I played one of the best matches of my career," said Anderson. "To do it at this stage, at this round, to get through to the quarter the first time in a slam definitely means a lot to me."
"It feels good to take a little step and actually beat one of the best guys in the world in the fourth round of a slam.
"Playing Andy, who is a champion here (2012) ... I must say playing out there will be definitely one for the memory bank."
Roger Federer cut down big-serving American John Isner in straight sets at the US Open on Monday to claim an accustomed grand slam quarter-finals spot at Flushing Meadows.
The Swiss second seed, winner of a record 17 grand slam titles, beat 13th seed Isner 7-6(0), 7-6(6), 7-5 to set up a last eight clash against 12th-seeded Frenchman Richard Gasquet, who ousted sixth-seeded Czech Tomas Berdych in four sets.
The world number two will be contesting his 46th grand slam quarter-final.
Federer, who never lost his serve, held his own from the service line to thwart Isner and used his returning skills to derail a pair of long streaks enjoyed by the American.
The 34-year-old Federer closed out the two hour, 39 minute fourth-round match by breaking the six-foot-10-inch (2.08 metres) Isner's serve, ending the American's string of 108 consecutive service holds at the US Open, dating back to the beginning of last year's championship.
His perfect scoreline in the opening set tiebreak snapped an even longer Isner streak.
In 429 tiebreakers played by Isner, he had never dropped one 7-0.
"Seven-love obviously is a pretty good score against John," said Federer.
Simona Halep overcame a thigh injury, baking heat and finally big-hitting German Sabine Lisicki. It was Labor Day in the United States but it was certainly no holiday for Halep who had to work for her spot in the last eight, needing two hours and 38 minutes under a broiling sun to dispatch Lisicki 6-7(6), 7-5, 6-2 and reach the US Open quarter-finals for the first time.
It was a battle of wills between Halep and Lisicki to see who would be last woman standing.
After dropping the opening set Halep called out the trainer to have treatment on her left thigh and at the end of the second the players left the court when the heat rule came into affect, but through it all the exhausted Romanian was able to gut out a victory.
Her left leg heavily strapped, a wounded Halep sensed her opportunity when Lisicki began to cramp in the third set and stretch between every point.
Halep, who converted 10 of 11 break chances, claimed the most crucial one to go ahead 4-2 and then held serve to break her 24th seeded opponent again and clinch a spot in the last eight at Flushing Meadows.
Lisicki, who holds the women's record for fastest serve and most aces in a match, did not have her big weapon working on Monday as she managed just two aces in the entire match.
Waiting for the second seeded Romanian in the last eight is two-time US Open finalist Victoria Azarenka, who advanced with a comfortable 6-3, 6-4, win over American Varvara Lepchenko.
Italy's Flavia Pennetta returned to the quarter-finals for the fourth consecutive year easing past 2011 US Open winner Samantha Stosur of Australia 6-4, 6-4.
Czech fifth seed and double Wimbledon champion Kvitova saw off British qualifier Johanna Konta 7-5, 6-3.
Kvitova is the first Czech in the quarter-finals since Daja Bedanova in 2001.
American Donald Young's US Open fairytale ended with a fourth-round loss to Stan Wawrinka on Monday.
The 26-year-old Young, regarded during his teenage years as the next great American men's player, had advanced to the fourth round with two epic wins from two sets down but ran out of comeback magic against the fifth seed Swiss, surrendering 6-4, 1-6, 6-3, 6-4.
Fifth seed Wawrinka stayed on track for a last eight clash against big-serving South African Kevin Anderson who beat third seed Andy Murray.
The Swiss shut the door on the 68th-ranked Young by not allowing the American to reach a single break point in the fourth set.
"I think now he (Young) is more the player that he is. He's playing his game," said Wawrinka. "He's trying to play the way he wants. He's trying to do things. He's coming on the court knowing what he's going to try to do.
"Now we have to see how he's going to go from here also because we all know that in general when he's playing at home he's playing better than the rest of the tournaments."
