Fifth seed Robin Soderling fell victim to the highest-profile surprise of the men's draw so far as he lost 6-1 6-4 7-5 to Australian teenager Bernard Tomic.
The Swede felt sick and dizzy as he lost the opening set of their third-round match in only 17 minutes.
Tomic, 18, kept firing groundstrokes as he secured the solitary break of the second set in its fifth game.
The upset was complete when the qualifier stole ahead late in the third before holding his nerve to serve out.
"I had to play very well to win," Tomic told BBC Sport in the wake of his victory.
"It is probably the greatest achievement of my career so far, I'm really happy.
"I looked very calm but inside I was bursting. I could see he was getting frustrated and I tried not to show it to him.
"I will always remember this as the first time I have really done well at a Grand Slam.
"It is a new experience for me playing the second week. It has been weird but I'm sure I'll get used to it.
"I think I can win in the next round. I have to go out there and believe like I did today."
Soderling confirmed that he had struggled after feeling unwell for a couple of days before the match.
"I didn't feel so good on court. I wasn't moving well I was misjudging a lot of balls. " said Soderling.
"I felt sick, I felt weak and I felt dizzy. It just wasn't a good day.
"He played a pretty good first set but i was more worried about myself and finding my game."
Tomic, whose best previous run in a Grand Slam ended in a third-round defeat by world number one Rafael Nadal at the 2011 Australian Open, will play Xavier Malisse in the last 16.
The German-born right-hander began the tournament 153 ranking places adrift of Soderling, but the gap is certain to close after a crowd-pleasing win on Court One.
Soderling regularly motioned up to the players' box, apparently suffering with a problem with his vision, as the opening set slipped away in startling fashion.
His complaints became less frequent and his play improved in the second set, but another unforced error, as he netted a regulation shot at break point, allowed Tomic to move ahead again.
Soderling had recovered from two sets adrift to overhaul Tomic's countryman Lleyton Hewitt in the previous round, but he could not repeat the trick as Tomic faced down two break points to seize the final game and the match.
The win will take Tomic above Hewitt in the rankings, ending the 30-year-old's 11-year reign as Australian number one.
Tomic's next opponent, Belgian Malisse, was another surprise winner.
The unseeded 30-year-old ousted 11th seed Jurgen Melzer 7-6 6-3 6-0.
Ninth seed Gael Monfils was also sent crashing out of Wimbledon, beaten 6-3 3-6 6-3 6-3 by qualifier Lukasz Kubot.
Their match resumed on Court Three at one set all and 3-3 on Saturday after being bit by bad weather on Friday.
Juan Martin Del Potro set up a clash with defending champion Rafael Nadal after knocking out 15th seed Gilles Simon 7-6 (10-8) 7-6 (7-5) 7-5.
The 6ft 6in Argentine won to love on his service to seal victory, smashing a 126mph ace to finish off the Frenchman.
Nadal, who beat Luxembourg's Gilles Muller to reach the fourth round, said of Del Potro: "He's a fantastic player, one of the best in the world.
"He had an important injury last year, but he's here now and he's at his top level."
Tomas Berdych, last year's beaten Wimbledon finalist, cruised into the fourth round with an easy win over Alex Bogomolov Jr.
The sixth seed from the Czech Republic saw off his American opponent 6-2 6-4 6-3 on Court 18.
Bogomolov Jr said: "Thomas got to the final last year for a reason. He's playing really well on grass and hitting some incredible shots on the run."
In the fourth round, Berdych will face another American, 10th seed Mardy Fish.
Fish progressed after third-round opponent Robin Haase of the Netherlands retired with an injury, with the score at 6-3 6-7 (5-7) 6-2 1-1.
Kubot, who won three qualifying matches to get into the main draw and also reached the last 16 at the 2010 Australian Open, next plays Spain's Feliciano Lopez.
Spanish seventh seed David Ferrer eased into the second week with a 6-4 6-3 6-3 win over Slovakia's Karol Beck, and he now plays Jo-Wilfried Tsonga.
French 12th seed Tsonga had a similarly comfortable passage into the fourth round, beating Fernando Gonzalez of Chile 6-3 6-4 6-3.
Tsonga's compatriot Michael Llodra, seeded 19th, will face second seed Novak Djokovic next after overcoming Yen-Hsun Lu 6-3 6-3 6-1.
Eighteenth seed Mikhail Youzhny will take on six-time champion Roger Federer after recovering from the loss of the opening set to grind out a 4-6 6-3 7-6 (7-3) 6-3 victory over Spain's Nicolas Almagro.