WIMBLEDON, England - Six-time champion Roger Federer was upset in the Wimbledon quarterfinals for the second straight year Wednesday, squandering a two-set lead for the first time at a Grand Slam tournament and losing to Jo-Wilfried Tsonga 3-6, 6-7 (3), 6-4, 6-4, 6-4.

Tsonga will face second-seeded Novak Djokovic, who defeated 18-year-old Australian qualifier Bernard Tomic 6-2, 3-6, 6-3, 7-5. Defending champion Rafael Nadal also advanced, beating Mardy Fish 6-3, 6-3, 5-7, 6-4. The two-time champion will face fourth-seeded Andy Murray, who defeated Feliciano Lopez 6-3, 6-4, 6-4.

Federer barely looked challenged while winning the first two sets against the 12th-seeded Frenchman. But the Swiss star, who had been 178-0 in matches in which he had won the opening two sets at a major tournament, was broken one time in each of the last three sets.

"It's kind of hard going out of the tournament that way, but unfortunately it does happen sometimes," said Federer, who was playing in his 29th straight major quarterfinal. "At least it took him sort of a special performance to beat me, which is somewhat nice."

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Federer may be right. The 16-time Grand Slam champion finished the match with only 11 unforced errors, half as many as Tsonga, but it didn't help him get close to breaking Tsonga's serve when he needed it.

"I was two sets down and I break. I did a good game of return and after that it was just amazing," said Tsonga, who had 63 winners, five more than Federer. "I just played unbelievable, served unbelievable and now I'm here, I'm in semifinal and I can't believe it."

Federer was seeking to equal Pete Sampras' record of seven Wimbledon singles titles. He breezed through his opening four matches, losing only one set, and played his usual elegant game against Tsonga.

In the first set, Federer earned his one and only break point of the match in Tsonga's first service game, and converted it. He held the rest of the way, and then won the second set in the tiebreaker.

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But Tsonga finally got his first break in the third set, and another in the fourth and another in the fifth.

"He can come up with some good stuff and some poor things at times," Federer said. "He had basically good return games along the way in the third, fourth, and fifth. I think especially the third set, the break I get is very unusual. He chips back a couple, they stay in."

Those were the Frenchman's only three breaks, and they were just enough to send Federer home early again.

Federer has won six titles at the All England Club, including five in a row from 2003-07. He lost to Nadal in the 2008 final in what is considered by many to be one of the greatest matches ever, and then beat Andy Roddick for the championship a year later, winning 16-14 in the fifth set.

Last year, he lost to eventual runner-up Tomas Berdych in the quarterfinals.

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"It's the biggest champion in my sport," Tsonga said. "He achieved a lot of things and he's just the best player in the world and I'm just so happy to win against him, especially on grass because it's maybe one of his favorite surface and I'm just so happy today."

Instead of Federer improving on his record haul of major titles, 10-time Grand Slam champion Nadal can add to his own.

The defending champion never seemed hampered by the foot injury that almost made him retire from his fourth-round match two days earlier, beating Mardy Fish 6-3, 6-3, 5-7, 6-4 Wednesday in the quarterfinals.

It was another display of power tennis from the Spaniard, although he was quick to credit powerful pain killers for the victory.

"My foot is not fine," the top-ranked Nadal said. "But we are in quarterfinals of Wimbledon. It's an emergency, so I had to play. So we decided to (numb) a little bit the zone of the foot to play the rest of the tournament, and that's what I'm going to do. ... When you (numb) the foot before the match, the anesthetic is for five hours, so you don't feel nothing."

It didn't show much either as Nadal ran along the baseline to hit numerous passing shots to counter the American's strategy of repeatedly attacking the net. He appeared to be cruising toward an easy victory after breaking Fish to start the third set before a momentary lapse let his opponent back into the match.

Nadal hit several uncharacteristic errors to help Fish break right back, and the American broke again in the 12th game, hitting a forehand winner down the right sideline on his second set point.

But Nadal wasn't about to let a two-set lead slip away.

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In the third game of the fourth set, he set up two break points with a perfect drop shot, and converted the first when Fish netted a forehand volley. He was never threatened after that and served out the match at love, finishing off his first match point with an easy volley.

He will now face Murray in the semifinals for the second year in a row, having beaten the Briton at the same stage at the French Open last month as well.

"I believe I can win against him. I had chances last year," Murray said. "I just have to have a better game plan. Sometimes it comes down to strategy. Sometimes it comes down to having more experience."

Murray is the only semifinalist to go through the last two rounds without dropping a set, and Nadal has been impressed with the Briton's play so far.

"Probably this year he has a little bit more experience," Nadal said. "He's playing very well, having (reached the) final in Australia, semifinals in Roland Garros, now semifinals another time here. So he's having a very successful season, in my opinion. So he's with big confidence. Anyway, the previous matches doesn't affect the match of Friday."