(CNN) -- Roger Federer crashed out of the U.S. Open after a surprise defeat at the hands of Czech sixth seed Tomas Berdych, ending the world No. 1's hopes of winning a record sixth title in the professional era.
Berdych won 7-6 (7-1) 6-4 3-6 6-3 in under three hours in Wednesday's evening session to reach the semifinals for the first time at Flushing Meadows.
"I just didn't come up with the goods tonight," said Federer, in quotes carried on the official tournament website, after his first match in four days following a walkover against American Mardy Fish.
"He probably created more than I did, and that's why he ended up winning."
Federer made his earliest exit in New York since 2003 and now has an 11-5 record against the 26-year-old -- who beat him at the 2004 Olympics and at Wimbledon in 2010, when he went on to lose in the final.
Berdych will face Olympic champion Andy Murray in the last four, after the Scot came back from a set down to oust giant Croatian Marin Cilic, winning 3-6 7-6 (7-4) 6-2 6-0.
Cilic, who will be left to rue a number of missed opportunities, surrendered a 5-1 lead in the second set.
This proved to be a turning point for the resurgent Murray, who finally found his rhythm as his confidence grew. All of a sudden, he had answers to the 12th seed's massive serve and booming forehand as he breezed through the next two sets to earn a place in the semis.
The match had been moved from the main Arthur Ashe Stadium to the Louis Armstrong court, and 2008 U.S. Open finalist Murray struggled in front of an initially small crowd against a player who beat him at the same tournament three years ago.
"You have to be able to create your own atmosphere when you're on the court, but I did play better when the crowd filled up," said Murray, still seeking his first grand slam title after losing to Federer in July's Wimbledon final.
"It's a quicker court. When you switch from one court to the other, it can take time to get into a rhythm. I have never played particularly well on that court."
Earlier, 2009 U.S. Open champion Juan Martin Del Potro brought the curtain down on Andy Roddick's glittering career by beating the home favorite in four sets in their rain-delayed fourth-round match on Arthur Ashe.
Roddick, the last U.S. male to win a grand slam when he triumphed in New York in 2003, announced last week that it would be his last tournament.
The former world No. 1 met his match against the seventh-seeded Argentinian, who will play defending champion Novak Djokovic in the quarterfinals.
When play resumed after being tied at 6-6 in the first set from Tuesday, Roddick took the tiebreaker but he could make no further progress against the 23-year-old Olympic bronze medalist.
There were no breaks of service in the second, but Del Potro took the tiebreaker and then proceeded to dominate, completing a 6-7 (1-7) 7-6 (7-4) 6-2 6-4 victory.
Roddick was visibly emotional in the final game on the Arthur Ashe Stadium Court and received a huge ovation from the crowd as he bowed out.
"Playing the last five games was pretty hard. Once I got down a break, I could barely look at my (players) box," Roddick said.
"I don't know what the emotions are. I'm a little overwhelmed right now. I normally feel like I can grasp things pretty quickly and clearly. I certainly don't feel that way right now."
World No. 2 Djokovic had easier progress, as his opponent Stanislas Wawrinka was forced to retire when trailing by two sets and 3-1 in the third.
The Swiss 18th seed complained of feeling ill as the rain-delayed match came to a swift conclusion.
"It's an unfortunate situation that happened with him, but I felt that I was hitting the ball well in the last two sets before that happened," said Djokovic, who reached his sixth successive U.S. Open quarterfinal, having dropped just 20 games in four matches.
"Hopefully I can keep that going for the next match."
His fellow Serbian, eighth seed Janko Tipsarevic, reached the last eight at Flushing Meadows for the second straight year as he eased past Germany's No. 19 Philipp Kohlschreiber of Germany 6-3 7-6 (7-5) 6-2.
He will next play Spanish fourth seed David Ferrer, who has been in equally fine form in the final grand slam of the season.