(CNN) -- Six-time champion Roger Federer has failed to make the title match at Wimbledon for the first time since 2002 after being dumped out in the quarterfinals on Wednesday.
Federer's title defense came crashing to a halt in the face of an inspired performance from Tomas Berdych in London.
The Swiss star was knocked out at the last-eight stage of a tennis grand slam event for second successive time following his similar exit at the French Open a month ago.
Czech 12th seed Berdych triumphed 6-4 3-6 6-1 6-4 in front of a stunned crowd on Centre Court to set up a semifinal clash with No. 3 Novak Djokovic.
Federer, the top seed ahead of world No. 1 Rafael Nadal -- who reached the semis by beating sixth seed Robin Soderling -- later revealed that he had been hampered by injuries.
"I am struggling with a little bit of a back and a leg issue. That just doesn't quite allow me to play the way I would like to play. So it's frustrating, to say the least," the 28-year-old star told reporters, as quoted by AFP.
"The leg injury came in the finals of Halle. That never really went away, and the back's been feeling really badly stiff for the last five or six days. When you're hurting, it's just a combination of many things. You just don't feel as comfortable.
"Under the circumstances, I think I played a decent match. But I've been feeling bad for the last two, three matches now. It's just not good and healthy to play under these kind of conditions. So if there's anything good about this, it's that I'm going to get some rest, that's for sure."
Federer was sluggish throughout the match, and though Berdych wobbled in the final games, he held his nerve to record the biggest victory of his career to date.
Berdych broke Federer's serve in the seventh game of the opening set to take it 6-4, but the world number two looked to have regained control as he powered to a 6-3 triumph in the second.
But Federer's game fell apart in the third set as Berdych took it 6-1 in just 27 minutes.
Another vital break in the fourth set took Berdych to the brink of victory, and he took his second match point to seal an impressive win.
It was only Federer's sixth defeat on Centre Court, but the former champion was still afforded a huge ovation as he waved to the crowd upon leaving the arena.
Berdych reached his second grand slam semifinal, having also reached the last four in Paris earlier this month before losing to eventual runner-up Soderling.
"It's amazing to play in this stadium against such a great player and to leave as the winner is an amazing feeling," he told the BBC.
"So far it was the toughest game in my career to serve to close out the match."
Earlier, Djokovic brushed aside the challenge of Yen-Hsun Lu to clinch a place in the last four.
The Serbian had little trouble dispatching Lu, from Taiwan, 6-3 6-2 6-2 in just one hour and 51 minutes on Court No. 1.
Djokovic's unseeded opponent, who beat American Andy Roddick in the previous round, didn't force a single break point in the entire match.
Djokovic told the BBC: "Nothing is easy these days especially at this stage of the tournament but the way I played I deserved to win. I hit all the shots, played the rallies and was solid from all parts of the court and I am very happy.
"I sincerely hope I can continue with this level of my game but you never know how you are going to wake up in two days but the way I am playing match after match is very encouraging.
"You have nothing to lose in the semifinals and definitely this time I am physically fitter than in my last one three years ago."
Nadal, who beat Federer in the final in 2008 but missed out on last year's event due to knee problems, was again too strong for Soderling as he followed up his Roland Garros triumph with another win over the Swede.
The Spaniard came from behind to win 3-6 6-3 7-6 (7-4) 6-1.
He will now face Andy Murray after the British fourth seed beat French No. 10 Jo-Wilfried Tsonga 6-7 7-6 6-2 6-2.
Murray dropped the opening set on a tie-break but took the second by the same method.
After that, Tsonga capitulated and Murray wrapped up the third and fourth sets with the minimum of fuss.
Speaking of his clash with Nadal Murray told the BBC: "It will be a great match, it's always fun. I think we've played four times in Grand Slams and won two each. I'm looking forward to it."