Struggling to run at full speed after requiring treatment to his legs, elbow and neck, a clearly frustrated Murray 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."
It 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.
"I'm very disappointed, obviously, but I think I've been more disappointed," Murray said.
"In other Grand Slams, when you get closer to winning the tournament, it becomes a lot harder to take."
Wawrinka, seeded 25th, advanced to play American Sam Querrey in the fourth round although the big winner could well be Rafa Nadal, who was drawn to face Murray in the semi-finals.
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