The World No 3 looked relatively comfortable until the end of the opening set, but was then brutally exposed by the brilliance of the Swiss in a 6-4 6-3 6-2 defeat in a blustery Arthur Ashe Stadium.
It was a lacklustre and error-strewn performance by the Brit 12 months after lifting the US Open trophy, but Murray paid tribute to his ninth-seeded-conqueror.
"I would have liked to have played a little bit better," Murray said. "When it's breezy conditions it's difficult but I've had a good run the last couple of years. It's a shame I had to play a bad match.
"I thought he played great. I made a few mistakes but for the most part he hit a lot of lines, he hit big shots and he played too well.
"When he had the wind with him he served very well and I had to do a lot of defending. Everyone takes a little time to feel comfortable on the court, but I didn't think I was playing poorly. I would have liked to play better.
"I thought there were a fair few long points, but I didn't get into enough return games, which was disappointing for me."
Murray conceded it had been a long road since he broke into the top, first at the Olympics on home turf last year, then with the two major titles.
"When you work hard at something for a lot of years, it's going to take time to fire yourself up and get to training 110%," the 26-year-old said about his preparation for the year's final Grand Slam.
"That's something kind of natural after what happened at Wimbledon. If I'm meant to win every Grand Slam I play or be in the final, it's just very, very difficult just now. With the guys around us, it's very challenging."
It was though a stunning show by Wawrinka who didn't even face a break point on his way to earning his first Grand Slam semi-final berth, producing 45 winners compared to 15 for his opponent.
"Andy Murray's the defending champion, he's a tough opponent. For me to get through in three sets is amazing," said the Swiss 28-year-old who will play top seed Novak Djokovic or Mikhail Youzhny for a place in the final.
"The first set was not easy. It was really windy today. To get that set gave me confidence for the rest of the match. So much was going through my head in the last game.
"I just try to be focused, to play solidly, aggressively, to take the match and not let him back. I'm going to relax a little bit, and then I'll watch the night session to see who wins."