It was a mixed day for seeds at the US Open as Caroline Wozniacki and Dominika Cibulkova bowed out but Garbine Muguruza won through to the third round and Maria Sharapova survived.
Former world number one and two-time US Open finalist Wozniacki lost in three sets to Ekaterina Makarova on Wednesday.
Cibulkova - the 2014 Australian Open runner-up and 11th seed - was also a notable casualty at Flushing Meadows, where Wimbledon champion and third seed Muguruza progressed beyond the second round of the tournament for the first time.
Returning five-time grand slam champion Sharapova survived, while fourth seed Elina Svitolina and 13th seed Petra Kvitova booked their spots in the next round.
WOZNIACKI FALLS TO MAKAROVA
One of seven women remaining in the draw in contention to claim the WTA's number one ranking, fifth seed Wozniacki lost 6-2 6-7 (5-7) 6-1.
Wozniacki had won all seven previous encounters with Makarova but that flawless run came to an end following Wednesday's thriller.
A semi-finalist in 2014, Makarova will face Carla Suarez Navarro.
Cibulkova, meanwhile, went down 6-2 5-7 6-3 to Sloane Stephens.
MUGURUZA POWERS ON
The Spanish star was tested early but eased to a 6-4 6-0 victory over Duan Yingying.
It was a slow start by Muguruza, who stormed out of the blocks in the second set, breaking on three occasions as she won the final nine games of the match.
Muguruza will play 31st seed Magdalena Rybarikova for a place in the last 16.
Venus Williams, Australian Open semi-finalist Coco Vandeweghe, Agnieszka Radwanska and Dario Gavrilova were among the other seeds to progress.
SHARAPOVA COMPLETES COMEBACK
The Russian showed grit and determination in her 6-7 (4-7) 6-4 6-1 win against Timea Babos.
After upstaging Simona Halep in her grand slam return following a 15-month doping ban, 2006 US Open winner Sharapova stayed alive as she rallied past her Hungarian opponent.
Next up for Sharapova is Sofia Kenin.
MLADENOVIC DIPS FURTHER
After the high of making just her second grand slam quarter-final at the French Open, Kristina Mladenovic has endured a disappointing slump in form.
Since sustaining knee ligament damage from a fall at Wimbledon, the Frenchwoman - seeded 14th at Flushing Meadows - has won just one of six matches, the latest a 6-3 6-2 loss to Monica Niculescu in Wednesday's first-round match.
"There are highs and lows in a season. I had a complicated Wimbledon where I pulled a ligament in my right knee," she said. "It's frustrating, but it's part of an athlete's life ... it's a process."
Eugenie Bouchard was also eliminated at the first hurdle, defeated by Evgeniya Rodina 7-6 (7-2) 6-2.
KUZNETSOVA SAVES THREE MPS
Svetlana Kuznetsova emerged from the clutches of defeat to prevail 4-6 6-4 7-6 (7-2) against Marketa Vondrousova.
The Russian eighth seed saved three match points to move into the second round.
"I think it was crazy," Kuznetsova. "Yesterday [Tuesday], I was in the locker room talking to Andrea Petkovic, saying how I'd played Naomi Osaka in China last year. I won, facing match points.
"She said, 'Yeah, you always have these kind of matches. I'm like, 'No, no, no. I just had this one.' She said, 'No, Riske, this year.' I said, 'Yeah, but that's it.' It's typical. When these talks happen, that's when it happens to you."