Chinese star Li Na crashed out of Wimbledon on Friday in another twist to her love-hate relationship with the tournament while Novak Djokovic and defending champion Andy Murray reached the last 16.
But five-time women's champion Venus Williams, men's 2002 winner Lleyton Hewitt and 2010 runner-up Tomas Berdych all made their exits.
Second seed Li lost 7-6 (7/5), 7-6 (7/5) in the third round to Barbora Zahlavova Strycova of the Czech Republic with the defeat coming hot on the heels of her shock first round exit at the French Open.
In eight appearances at Wimbledon, the 32-year-old Li has still never got beyond the quarter-finals.
She admitted she blundered by not playing a grasscourt warm-up, but was discouraged by the prospect of having to compete on the wet and wild English south coast.
"I always play Eastbourne every year, but it's always raining and windy. So I said, OK, I cannot practice in that," she said.
"I said let's change a little bit. I came here pretty early to try and play on the grass courts. It was the wrong decision."
Victory for Zahlavova Strycova represented a first last-16 spot at a major for the world number 43 at the 32nd time of asking.
Top seed Djokovic survived a shoulder injury scare to reach the fourth round for the eighth time with a 6-4, 6-2, 6-4 win over Gilles Simon, his seventh straight victory over the Frenchman.
Djokovic, the 2011 champion, needed a medical timeout to receive treatment and take a painkiller after hurting his left shoulder in a spectacular diving attempt to reach a Simon drive in the sixth game of the third set on Centre Court.
But the Serb recovered to set up a clash with French 14th seed Jo-Wilfried Tsonga for a place in the quarter-finals.
"It was a sharp pain when I fell. There was no damage in the joint, so I could play a few games after that. The muscle was still quite sore because of the impact," said the world number two.
Tsonga made the last 16 by beating Jimmy Wang of Taiwan, 6-2, 6-2, 7-5.
Murray, who eased to a 6-2, 6-3, 6-2 win over Spanish 27th seed Roberto Bautista Agut, has made the last 16 for the loss of just 19 games, beating his previous Wimbledon best of 26 games conceded in 2010.
He will face Kevin Anderson, the first South African to reach the fourth round for 14 years, after he clinched a 4-6, 6-4, 2-6, 6-2, 6-1 victory over Italian 16th seed Fabio Fognini.
Murray said: "It's been a good first week. I had plenty of long matches at the French Open to get me physically ready for this."
- Berdych, Hewitt, Venus all out-
Both Djokovic and Murray saw one of the dangermen in their half of the draw removed when sixth seed Berdych was knocked out by Croatia's 26th seed Marin Cilic, 7-6 (7/5), 6-4, 7-6 (8/6) in a match which finished after 21:30 local time (22:30GMT).
Cilic will face Jeremy Chardy of France for a quarter-final place.
Australian veteran Hewitt played a record 42nd five-set Grand Slam match but still went down in a delayed second round tie, losing to 2013 semi-finalist Jerzy Janowicz of Poland, 7-5, 6-4, 6-7 (7/9), 4-6, 6-3. Janowicz faces Spanish 23rd seed Tommy Robredo in the third round.
In her 17th Wimbledon and 63rd Grand Slam, Williams lost 5-7, 7-6 (7/2), 7-5 in the third round to 2011 champion Petra Kvitova, the sixth seeded Czech, who next plays China's Peng Shuai.
Bulgarian 11th seed Grigor Dimitrov won a marathon battle with Alexandr Dolgopolov of the Ukraine 6-7 (3/7), 6-4, 2-6, 6-4, 6-1 to make the last 16 for the first time.
He will face unseeded Argentine Leonardo Mayer who beat Russian qualifier Andrey Kuznetsov 6-4, 7-6 (7/1), 6-3.
Former women's world number one Caroline Wozniacki reached the last 16 for the fourth time with a 6-3, 6-0 win over Croatian 16-year-old Ana Konjuh, the world number 189.
Belinda Bencic, the reigning Wimbledon girls' champion, won her delayed second round tie 6-4, 7-5 against America's Victoria Duval.
The 17-year-old Swiss next faces third-seeded Simona Halep of Romania, the French Open runner-up, who clinched a 6-3, 4-6, 6-4 win over Ukrainian qualifier Lesia Tsurenko.