Roger Federer moved a step closer to an elusive Olympic singles gold after reaching the final eight but Israel's Jonathan Erlich and Andy Ram ended the world number one's hopes of repeating his Beijing doubles success.
Venus Williams' hopes of becoming the first tennis player to win four Olympic gold medals will have to rest on the doubles after she was knocked out of the women's singles in a 7-6 7-6 third-round defeat to Germany's Angelique Kerber.
Top seed and 17-times grand slam champion Federer overcame a shaky moment against Uzbekistan's Denis Istomin, saving three break points at 5-5 in the first set before securing his place in the quarter-finals with a 7-5 6-3 win on Wednesday.
Returning to court later with doubles partner Stanislas Wawrinka he was less successful however, as his starstruck opponents overcame their awe to eliminate the Swiss gold medallists 1-6 7-6 6-3.
"We struggled at the beginning, we were a bit excited to be playing on the same court as the best player in the world," said Erlich, who was keeping his eyes on the prize. "We came here to go all the way and not just to beat Federer."
Men's number two seed Novak Djokovic struggled into the singles quarter-finals with a 4-6 7-5 6-1 win over world number 158
Australia's Lleyton Hewitt while Britain's Andy Murray also came from behind to claw back a 4-6 6-1 6-4 win over Cypriot Marcos Baghdatis.
Fourth seeded Spaniard David Ferrer did not manage the same feat in his clash against Japan's world number 18 Kei Nishikori however, losing 6-0 3-6 6-4 in a match finished under the floodlights of Centre Court.
Earlier, Centre Court rang out with cries of "Aussie, Aussie, Aussie, oi oi oi" as Beijing bronze medallist Djokovic was given a run for his money by Hewitt, who won Wimbledon in 2002 but has since been plagued by injury.
Having had the first set snatched from him, the rattled Serb went 5-3 ahead in the second. Although a valiant Hewitt levelled the score at 5-5, Djokovic broke again to force a decider.
Djokovic, who at one point entertained the lively crowd with a shot through the legs, found his stride in the third, breaking the 31-year-old twice to serve for the match at 5-1.
As Hewitt, who was given his place at the Games by the International Tennis Federation, hit a backhand into the net to hand Djokovic the victory, the 25-year-old pumped his fists in the air before letting out a big sigh of relief.
"Incredible match," the five-times grand slam winner said.
"It's never that easy against Lleyton, he's one of the best returners ever to play the game. It was a great test... and I look forward to the next challenge."
That challenge will be Jo-Wilfried Tsonga, who he will play for a place in the semi-finals after the Frenchman mustered enough energy to beat Spain's Feliciano Lopez 7-6 6-4 less than 24 hours after his second-round win over Milos Raonic set the record for longest three-set match in Olympic tennis.
There was another record-breaking match on Wednesday, with fifth seeded Czechs Tomas Berdych and Radek Stepanek losing their second-round clash against Brazil's Marcelo Melo and Bruno Soares 1-6 6-4 24-22 in four hours, 21 minutes.
The 63-game match, which had been stopped at 18-18 in the final set as the light faded on Tuesday, was the longest three-set men's doubles match and the third set the longest men's doubles set in Olympic history.
Hewitt made up for his earlier singles exit with a win in the mixed doubles event, which returns to the games after an 88-year break. He and Sam Stosur beat fourth seeded Polish pair Agnieszka Radwanska and Marcin Matkowski 6-3 6-3.
In the women's singles Serena Williams ploughed to a 6-1 6-0 win over Russia's Vera Zvonareva, who left the court in tears after the 51-minute annihilation.
She was soon joined by team mate Nadia Petrova, who was beaten 7-6 6-4 by Belarusian top seed Victoria Azarenka.
Belgium's Kim Clijsters, who plans to retire for the second time after September's U.S. Open, enjoyed a 6-3 6-4 win over 11th seeded Serbian Ana Ivanovic.
"I feel like I've been playing some really good tennis in the first three matches here, it's just a matter of trying to keep that up and before every match I need to refocus and stay on target," Clijsters, playing at her first and last Olympics, told reporters.
"When things go tough, fight each shot and that's all you can do... keep fighting and give it your all," added the 29-year-old.