WIMBLEDON, England - For two superb sets Wednesday, everything looked so routine for Roger Federer, precisely the way it did for so many years at Wimbledon - and nearly everywhere else, too.

Little comes easily for Federer anymore, even at the All England Club, where he's won six of his record 16 major championships.

Before Wednesday, Federer was 178-0 when taking the first two sets of a Grand Slam match.

Now he's 178-1.

Facing a younger, quicker and better-serving opponent, Federer failed to make his big lead stand up and lost 3-6, 6-7 (3), 6-4, 6-4, 6-4 to 12th-seeded Jo-Wilfried Tsonga of France in the quarterfinals. Federer leaves Wimbledon in that round for the second consecutive year, after reaching seven finals in a row from 2003-09.

Nevertheless, Federer sounded defiant in defeat, saying he played well against Tsonga and is sure he "definitely can" add to his Grand Slam collection, even though he'll turn 30 in August.

"When I was 20, I would have been crushed: 'I can't go on; I'll never get another chance to be in a quarterfinal of a Grand Slam.' But today, I know that I should probably have lots more," said Federer, who lost in the French Open final earlier this month. "I don't have that mental stress. I know what I've accomplished already. It's different when you're older and you've accomplished as much as I have."

The third-seeded Federer's loss prevented the 125th edition of Wimbledon from being the first since 1995 with the four top men in the semifinals.

The other favorites all won Wednesday, though not without some difficulty: No. 1 Rafael Nadal numbed his injured left foot with a painkilling injection then beat No. 10 Mardy Fish of the United States 6-3, 6-3, 5-7, 6-4; No. 2 Novak Djokovic was a break down in the third set but reeled off seven games in a row to get past 18-year-old qualifier Bernard Tomic of Australia 6-2, 3-6, 6-3, 7-5; and No. 4 Andy Murray pulled up awkwardly after tweaking his hip changing directions on one third-set point but otherwise breezed past unseeded Feliciano Lopez of Spain 6-3, 6-4, 6-4.

"There are other players that are able to play great tennis, and Tsonga has proved it today," said Djokovic, who would replace Nadal at No. 1 in the ATP rankings by reaching the final. "It's all very close at this level, especially in the second week of a Grand Slam."

In Friday's semifinals, Tsonga will face Djokovic, who is 46-1 in 2011, the only loss coming to Federer at the French Open. Defending champion Nadal will play Murray, who hopes to give Britain its first men's title at the All England Club in 75 years.

Although Fish thought Nadal moved well against him and showed no sign of injury, the 10-time major champion said: "My foot is not fine. But we are in quarterfinals of Wimbledon. Is an emergency, so I had to play."

Nadal is on a 19-match winning streak at the grass-court Grand Slam, and is 31-2 since the start of the 2006 tournament; both losses were against Federer in finals.

He's 11-4 against Murray, including a victory in last year's Wimbledon semifinals.

"You get pushed more and more as the rounds go on," said Murray, a three-time major runner-up. "I'm sure in the next round, I'm going to get pushed even harder, and I'm going to have to up my game again."

Federer, meanwhile, remains one Wimbledon trophy short of the men's record of seven, shared by Pete Sampras and Willie Renshaw, whose titles came in the 1880s.

"I thought my game was plenty good enough this year to win the tournament," Federer said. "Unfortunately, there's only one that can win it, and the rest go home empty-handed. That's what happened to me today. Jo played an amazing match."

That certainly is true.

Tsonga lost the first game he served - and then didn't face a break point the rest of the way. He finished with an 18-17 edge in aces and a 63-57 edge in total winners. And Tsonga managed to break Federer's serve once in each of the last three sets.

Most impressive of all, Tsonga hung in there even after falling so far behind.

"I was feeling really strong because I never - how you say that? - panic. I was, all the time, really focused," Tsonga said. "I was not scared on big points."

The 26-year-old Tsonga reached the 2008 Australian Open final before losing to Djokovic, who won that tournament again this year. But what appeared to be a rapid rise for Tsonga stalled, in part because of injuries to both knees.

He split with his coach in April and has yet to hire another. What Tsonga does not lack at the moment is self-belief.

Asked if he thinks he could win Wimbledon this year, Tsonga replied: "Um, why not?"

Wednesday's match was only his fifth career major quarterfinal; Federer has been at least that far at each of the past 29 Grand Slam tournaments. But after getting to the semifinals at a record 23 consecutive majors, Federer now has lost in the quarterfinals at three of the past five.

Inevitably, a reporter wanted to know whether Federer felt as if this were the end of an era.

"No, I don't think so," Federer said. "Wasn't a shocker, second-round loss in straight sets, some stupid match I played. It was a great match, I think, from both sides."

The quality was high, the exchanges entertaining. According to the official statistics, 120 points ended on winners by one man or the other - and only 33 ended on unforced errors. The highlight might have been a 25-stroke point in the second set's 10th game: After diving to his right for a volley that Federer tapped back, Tsonga tried in vain to jump headfirst to his left. He wound up chucking his racket in the ball's direction and belly flopping, then stayed prone on the court, face down and motionless, for several seconds, as Centre Court spectators rose to their feet, applauding the effort.

The fans gave another standing ovation before Tsonga came out to serve for the match in the fifth set. Perhaps they were saluting both players, but it felt as if they were telling Federer, "Thanks for the memories."

Tsonga had started turning things around by ripping a forehand passing winner to break Federer for the first time and take a 2-1 lead in the third set. Tsonga broke to 2-1 in the fourth with another forehand winner, then jogged to the sideline with his right fist aloft. The final break came in the fifth set's opening game, when Federer put a forehand into the net.

"I'm the kind of player," Tsonga said, "who likes these big moments."

For so long, that was an apt description of Federer. But he could not get back into this match, because Tsonga wouldn't let him. Tsonga won 40 of 49 points in his service games over the last two sets, closing the match with service winners at 135 mph, then 133 mph.

When it ended, Tsonga dropped to his knees at the baseline, then did his usual victory celebration, hopping across the court and shaking his fists near his head.

"It's not just his backhand or forehand or serve or physical or mental game - at the end, it's an overall effort. He was very strong. On the big points, he played his best, he took chances and risks," Federer said. "It's hard to accept, because I thought I was at least as good as he was."