Wimbledon champion Petra Kvitova became the latest big-name casualty at the US Open but Serena Williams continued her march through the draw.
The two-time defending champion made it a hat-trick of victories over fellow Americans with a 6-3 6-3 win against Varvara Lepchenko while Kvitova lost 6-4 6-4 to qualifier Aleksandra Krunic.
Kvitova much prefers the quiet of Wimbledon to the hustle and bustle of New York and she has never been beyond the fourth round at Flushing Meadows.
Her first two performances had raised hopes that she could break her hoodoo this time, but she could not break down the stubborn Krunic and lost 6-4 6-4.
The 21-year-old Serbian, ranked 145th, had never won a grand slam match before this tournament, but followed up her upset of Madison Keys with an even bigger scalp.
Kvitova, who had her right thigh heavily strapped, looked to have turned things around when she battled back from 4-2 down to 4-4 in the second set, but Krunic upped her game again.
When Kvitova sent her final forehand wide, the Serbian fell to the ground in celebration.
"I still cannot believe I won against Madison, and now I won against Petra," said Krunic. "So many things are happening in my mind.
"I'm trying to believe it, but when I believe it I'm afraid that I'm going to have so much emotion. I'm trying to keep it all together. My coach is already screaming and jumping, and I'm trying to stay away from him."
Kvitova praised Krunic's performance, saying: " I think she played really unbelievable tennis and she put a lot of balls back - almost all of them.
"For me it was very difficult just to play only on the winners. I did mistakes and I was really trying everything that I could in that moment. It was so difficult. It wasn't really my day.
"I did better than 2011, so that's good. That's tennis. Sometimes you're up, sometimes you are down. You wake up in the next morning and try to work hard again."
There are now only five of the top 10 women's seeds left in the tournament, with Kvitova joining Simona Halep, Agnieszka Radwanska, Angelique Kerber and Ana Ivanovic in falling early.
Krunic next faces two-time runner-up Victoria Azarenka, who hammered Elena Vesnina 6-1 6-1 and looks to be playing herself into form at the right time after an injury-hit season.
Azarenka said of Krunic: "S he obviously is playing great tennis and is really inspired here, winning so many matches in a row and upsetting such a great player. So it's going to be tough. I think it's always tricky when you don't know your opponent."
Williams had easily beaten Taylor Townsend and Vania King but certainly did not have things all her way against the impressive Lepchenko.
The world number one had to battle extremely hard in the second set in particular and next meets Estonia's Kaia Kanepi, who upset 15th seed Carla Suarez Navarro.
Williams and Lepchenko are good friends and the top seed said: "I love practising with her. We always practise together at tournaments. I think it helps her game and she helps my game.
"She gives 100 per cent on the court. She always tries to do her best. She's great. She is an incredible fighter."
The windy conditions did not help, and Williams said: " I definitely had to fight to find my rhythm.
"At the same time she was playing really well. She was going for shots, getting so many balls back. It wasn't all about my shots, she just got them back and hit a better shot at times. For me, it was just about hanging in there."
Eleventh seed Flavia Pennetta was a semi-finalist last season and is enjoying another good run, beating American Nicole Gibbs 6-4 6-0.
In the fourth round the Italian faces Australian Casey Dellacqua, who has risen almost 100 places in the rankings this year and defeated Ana Ivanovic's conqueror Karolina Pliskova 6-3 3-6 6-4.
Seventh seed Eugenie Bouchard survived another scrap to beat Barbora Zahlavova Strycova 6-2 6-7 (2/7) 6-4.
In her first night session match against Sorana Cirstea two days ago, Bouchard was pushed all the way and it was no different this time.
There is no doubting the mental toughness of the 20-year-old Canadian, though, and she showed it once again despite looking in big trouble in the third set.
Zahlavova Strycova led 30-0 on her serve at 4-4 having just broken Bouchard but she tightened up and paid for it dearly.
Bouchard, who next plays 17th seed Ekaterina Makarova, said: "I feel like I pulled myself together at the very, very end tonight.
"She got a lot of balls back. She made me work for it. At the same time she would occasionally come to the net, mix things up.
"It was the kind of variety I haven't seen much of. Generally most opponents don't do that so it was a little different.
"But I'm just proud at least that I could battle. Even if it's a little bit ugly or I don't feel great, I can still pull it out, which made me happy."