New York, United States: Alexander Zverev slumped to a last-16 defeat at Flushing Meadows on Monday while Rafael Nadal was set to battle Marin Cilic later in a clash of former US Open champions.
Sixth seed Zverev rolled through the opening set against Argentina's Diego Schwartzman under the roof on a rainswept Labor Day at Arthur Ashe Stadium, but lost his way to go down 3-6, 6-2, 6-4, 6-3.
The German was enjoying his deepest run in New York but committed 17 double faults and 65 unforced errors and received a point penalty for swearing as Schwartzman advanced to a second US Open quarter-final in three years.
"I think Alex had many problems with the serve. I'm a big returner and I took many chances and I think I played great tennis," Schwartzman said.
Zverev lost his serve three times during the second set but appeared to have steadied himself when he moved a break ahead at 3-2 in the third, only for Schwartzman to wrest the momentum back in his favor after a lengthy sixth game.
"It was tough because I was feeling I had the chance to win this and I had a few break points I could not take," Schwartzman said. "He was up a break and then I recovered really quickly and I felt great after that."
Schwartzman, also a quarter-finalist at last year's French Open, matched his best Grand Slam run and awaits the winner between 18-time major champion Nadal and Croatian 22nd seed Cilic.
Nadal, a three-time US Open winner, has spent barely four hours on court in reaching the last 16, having benefited from a walkover in the second round.
Cilic, the 2017 Wimbledon finalist, withstood 40 aces from John Isner in round three but has defeated Nadal just twice in eight attempts.
"I've played quite a few times with Rafa. When you play these top guys you have to come up with your great tennis," Cilic said.
Matteo Berrettini became just the second Italian man to progress to the US Open quarter-finals, 42 years after Corrado Barazzutti's run to the last four in New York.
Berrettini, the 24th seed, eased to a 6-1, 6-4, 7-6 (8/6) win over Russia's 43rd-ranked Andrey Rublev to reach the last eight at a Grand Slam for the first time.
"It's something really crazy. I cannot believe it right now. I need a few hours to understand what happened," said Berrettini, 23, who goes on to play French 13th seed Gael Monfils or Spaniard Pablo Andujar.
"I'm just happy. Seeing my team and family here and crying, for me it's unbelievable."
Berrettini went one step further than his run to the last 16 at Wimbledon in July, where he was beaten by Roger Federer.
The Italian overcame a momentary lapse against Rublev as he dropped serve at 6-5 in the third set but sealed victory after two hours and 11 minutes in a tense tie-break.
"I think I did an unbelievable match. I thought Andrey was playing really good and playing with confidence," Berrettini said.
"I was mixing my tennis, using the slice, forehand and serve. I think all my weapons were really good today."
Andujar, 33, will try to become the oldest player in the Open era to reach his first Grand Slam singles quarter-final as he battles Monfils, a semi-finalist at Flushing Meadows three years ago.