Top seeds Novak Djokovic and Serena Williams advanced as expected but the upset-riddled US Open women's draw took another hit when Wimbledon winner Petra Kvitova was ousted by a 145th-ranked qualifier on Saturday.
Kvitova, the third seed, joined the long upset hit-list at the hands of little-known, 21-year-old Aleksandra Krunic of Serbia, becoming the tournament's fifth victim among the top eight women's seeds.
Kvitova, outsteadied by the quick-moving Serb, joined Simona Halep (2), Agnieszka Radwanska (4), Angelique Kerber (6) and Ana Ivanovic (8) in being shown the exit.
World number ones Djokovic and Williams restored order with a pair of straight-set wins as a humid day at Flushing Meadows turned windy and cool.
Djokovic made another routine step in his bid to reach a fifth successive U.S. Open final by beating American Sam Querrey 6-3 6-2 6-2, taking 85 minutes to reach the round of 16. He has yet to lose a set.
The Serb, married three days after his Wimbledon triumph and expecting to become a father in two months, won only one match in each of his warm-up events prior to the Open but believes he is now hitting his stride.
"It's peaking at the right time, at the right tournament," he said. "This is where I want to play my best tennis. I didn't know how emotionally drained I was in a way until I played (Jo-Wilfried) Tsonga in Canada and played some great match and I didn't feel I could deliver my best. That's something that when I analyzed...was normal in a way."
Djokovic will next meet either big-serving American and 13th seed John Isner or 22nd seeded German Philipp Kohlschreiber.
Williams faced the toughest test yet in her US Open title defense before advancing with a hard-played 6-3 6-3 win over Varvara Lepchenko.
World number one Williams, who lost a total of five games in her first two matches, battled 95 minutes against the left-hander, the third fellow American she has met in the tournament.
"My opponent today was spectacular. It was really a good match and it just shows how far Varvara has come, so I'm really proud of her," Williams said about her frequent practice partner.
Williams was level 3-3 before running off the last three game of the opening set. Tied again at 3-3 in the second set, the 32-year-old, 17-times grand slam singles winner repeated the feat to claim victory over the 52nd-ranked Lepchenko.
Next up for Williams will be 50th-ranked Kaia Kanepi of Estonia, a 7-5 6-0 upset winner over 15th seed Carla Suarez Navarro of Spain.
The stunner of the day was registered by 21-year-old Krunic, who fell onto her back in celebration as well as exhaustion after a last groundstroke by the error-prone Kvitova sailed wide for the final point in the 6-4 6-4 shocker.
The diminutive Krunic, a blur as she sprinted and slid into splits stretching for returns, was as surprised as anyone.
"It was an honor for me to be on the same court as Petra, who is a great champion," Krunic told the Louis Armstrong Stadium crowd after the 98-minute match. "I watched both of her finals matches at Wimbledon. Going to play against such a champion meant to stay on the court as long as possible. Of course, I didn't expect to win. Of course, I hoped to. I'm very happy."
Krunic, who aims to graduate from university in Serbia this year with a degree in economics, calculated her chances were best by concentrating on keeping the ball in play.
Extending rallies with bursts of speed that often took her from the forehand corner to the backhand border, Krunic drew 34 errors from the left-hander while committing just 14.
Kvitova tried to seize control, unleashing 33 winners to only 17 from Krunic, but failed.
"I'm very disappointed," said Kvitova. "I think she played really unbelievable tennis and she put a lot of balls back. Almost all of them."
Krunic's victory ensured the Singidunum University student a payday of at least $187,000, more than triple her tennis winnings of $45,000 this year.
Her next test will come against another grand slam champion, twice Australian Open winner Victoria Azarenka of Belarus, who routed Russian Elena Vesnina 6-1 6-1.
Eighth seed Andy Murray, the 2012 Open champion and 2013 Wimbledon winner, double-faulted to send his match to a fourth set, then swiftly took charge in a 6-1 7-5 4-6 6-2 win over Russian Andrey Kuznetsov.
That set up a clash for the Scotsman against ninth seed Tsonga, a 6-4 6-4 6-4 winner against Pablo Carreno Busta of Spain.
Fifth-seeded Canadian Milos Raonic won three tiebreakers in a straight-set win against Dominican Victor Estrella Burgos to set up a fourth-round duel with Japan's 10th seed Kei Nishikori, who beat 23rd seed Leonardo Mayer of Argentina in straight sets.
Australian Open winner Stan Wawrinka was given a walkover into the fourth round when Blaz Kavcic of Slovenia defaulted because of a right foot injury.