By Julian Linden
Struggling to run at full speed after requiring treatment to his legs, elbow and neck, the Briton appeared powerless to stop Wawrinka, who was battling his own injury problems but still played superbly, from pulling off the biggest upset of the championship.
"I was struggling physically and I got frustrated with that," Murray said.
"Maybe I felt like my chance of doing well here was slipping away. I've worked very hard to give myself a chance of winning tournaments.
"It happens to everyone in life at different points."
Murray's limp departure was in stark contrast to an incredible fightback from Australia's Samantha Stosur, who saved four match points to beat Elena Dementieva 6-3 2-6 7-6 in a nail-biting center court match that did not end until 1.35 am (0535GMT), the latest finish for a women's match at the U.S. Open.
"That's definitely one of the most exciting match I've ever played. The atmosphere out there was just awesome," said Stosur.
"I think we both played a great match. It just came down to playing good tennis. We gave it our best shot."
The Spaniard, getting better with each match on the back of a new and improved serve, overpowered France's Gilles Simon 6-4 6-4 6-2 to steam into the fourth round without dropping a single service game in three matches.
"It was important not to lose without dropping a set," Nadal said. "Every day I seem to play much better which is good for my confidence."
The pair could hardly have been more impressive as they brushed past tricky opponents to remain on course for a blockbuster semi-final showdown when the season's last grand slam enters its second week.
"It's always good to have a tougher match, a kind of a match where you have to challenge yourself against your opponent and the conditions," said Williams, who played in a red sequined dress.
"You always want to do well at tournaments where you've done well, and obviously, the U.S. Open is a special tournament for me," Clijsters said.
"Tennis wise, I feel that I've been improving every match."
Clijsters' next opponent is Stosur, who is developing a reputation as one of the toughest players in women's tennis.
"I don't want to make a habit of doing this all the time," the fifth seed said.
"But it's amazing what experiences a week ago, a month ago, whatever, can really help you through the next one."
Nadal will face Lopez next with the winner to play either Ferrer or Verdasco.
"It's always nice to see all the Spanish winning and being in the last rounds," said Verdasco, who advanced with a four set win over Argentine David Nalbandian.
Wawrinka, seeded 25th, advanced to play Sam Querrey, the only American left in the men's competition, although the big winner could well be Nadal, who was drawn to face Murray in the semi-finals.
Murray's loss was another disappointment for the Scotsman, who arrived at Flushing Meadows seeded fourth, in great form, and holding genuine hopes of ending Britain's 74-year wait for a men's grand slam singles champion.
By the start of the third set he was clearly in discomfort and protecting his left thigh but did not ask for a medical timeout and allowed his frustrations to effect his game.
"I have no idea whether I'll win a grand slam or not," he said. "I want to, but if I never win one, then what?"
(Editing by Alastair Himmer)