German fourth seed Alexander Zverev wilted in 33-degree heat and crashed out in the third round on Saturday.
Zverev, playing for the third day in succession, was shocked by Latvian qualifier Ernests Gulbis, ranked 138, in a gruelling five sets, 7-6(2), 4-6, 5-7, 6-3, 6-0.
Three-time winner Novak Djokovic made the last 16 of a Slam for the 44th time with a 4-6, 6-3, 6-2, 6-4 win over Kyle Edmund, the last remaining Briton.
Despite being widely-tipped to be a Grand Slam threat, it was another let-down for Zverev whose run to the quarterfinals at Roland Garros last month remains his best performance at the Majors.
Gulbis, a former World No. 10 who famously defeated Roger Federer on his way to the French Open semifinals in 2014, will be playing in the last 16 at Wimbledon for the first time at the 11th attempt.
The 29-year-old will take on Japan’s Kei Nishikori who registered his 350th career win with a 6-1, 7-6(3), 6-4 victory over Australian Nick Kyrgios.
Gulbis’ win on Saturday was his third successive five-setter having also played three matches in qualifying.
Meanwhile, Roger Federer and Serena Williams will be expected to maintain their flawless progress as title favourites head into the fourth round on Monday looking to survive the tournament’s giant-killing carnage.
The status quo has been challenged like never before in the women’s singles, with nine of the top 10 seeds crashing out before the Wimbledon last 16 for the first time in the Open area.
Federer’s 175th win from 200 career grass-court matches has seen him overtake Jimmy Connors as the most successful male player on the surface. Next, the Swiss star faces French 22nd seed Adrian Mannarino for a place in the quarterfinals.
Federer’s tie is one of 16 fourth round matches across the men’s and women’s events in a frenetic day of action at the All England Club.
The 36-year-old Serena faces Russian qualifier — and fellow mother — Evgeniya Rodina in the last 16.
Karolina Pliskova, the seventh seed, is the only top 10 ranked player remaining, but she has never won a Major. The Czech faces Dutch 20th seed Kiki Bertens, who stunned five-time Wimbledon winner Venus in the third round.