Defending champion Roger Federer suffered his earliest exit at Wimbledon since 2002 with a second-round defeat by world number 116 Sergiy Stakhovsky.
Seven-time winner Federer, 31, lost 6-7 (5-7) 7-6 (7-5) 7-5 7-6 (7-5) on a dramatic day that had seen a record seven players retire through injury.
Federer and Jo-Wilfried Tsonga have now exited the competition to boost Andy Murray's title hopes.
Fifth seed Rafael Nadal was on Murray's side of the draw but lost in round one.
"You don't panic at this point, that's clear," said number three seed Federer, when asked about his future in the game.
"It's normal that after all of a sudden losing early, having being in Grand Slam quarter-finals 36 [straight] times, people feel it's different.
"But I still have plans to play for many more years to come."
Sixth seed Tsonga withdrew from his second-round match because of an injury, one of seven men and women to do so on day three.
Federer's defeat meant it was also his earliest Grand Slam exit since losing in the first round of the French Open in 2003.
It also ended the 17-time major champion's run of 36 consecutive quarter-final appearances in Grand Slam events, which started at Wimbledon in 2004.
"When you play Federer at Wimbledon it's like you're playing two people," said Stakhovsky, "Federer and his ego.
"I hoped he wouldn't get too far away from me and I hung in there every game on my serve, trying to play for a tie-break.
"It was magic, I couldn't play any better today. Every important point I played well and I served and volleyed incredibly well."
The 27-year-old Stakhovsky's previous best display at Wimbledon was reaching the second round in 2011 while he has never gone beyond the third round at a Grand Slam event.
And things started well enough for Federer, who edged a tight first set on a tie-break, before Stakhovsky took the second set tie-break to level.
Federer put pressure on his opponent's serve in the third set but could not find the breakthrough.
And he was made to pay when his own serve was broken in the 11th game, which constituted the first service break of the match.
Stakhovsky, who came to the net almost twice as much as Federer, moved to the brink of victory with an early break in the fourth set but Federer showed his class to level at 3-3.
He had set points on the Stakhovsky serve at 5-6 to take the match into a decider but his unheralded opponent stood firm to force another tie-break.
An early mini-break grew into a 5-2 lead for the Ukrainian and although Federer saved one match point with a courageous pass he faltered on the second, sending a backhand wide.
It was Federer's first defeat by a player ranked outside the top 100 since losing to 101-ranked Richard Gasquet at Monte Carlo in 2005.
It was also the earliest defeat for a defending Wimbledon men's singles champion since Lleyton Hewitt lost to Ivo Karlovic in the first round in 2003.