The defending champion Murray has made the Australian Open final and won at Wimbledon since he won his first Grand Slam title at last year's US Open, but his title defence is over after he was shocked in the quarter finals by Swiss No. 9 seed Wawrinka.
Murray had dropped just two sets in the first four rounds, one each against Leonardo Mayer and Denis Istomin, to appear on a collision course for yet another epic Grand Slam meeting in the semi finals with the world No. 1 Djokovic.
However, Wawrinka had other ideas as he now starts stealing some of the spotlight he has been hidden under in Switzerland with Roger Federer's dominance over the past decade.
It should have been no surprise that Wawrinka put up such an effort against Murray considering he had beaten former Australian Open finalist Marcos Baghdatis, Wimbledon finalist Tomas Berdych, giant Croatian Ivo Karlovic and Czech veteran Radek Stepanek on his way to the quarters.
That is quite the impressive list of opponents he had beaten in his first four matches with none of the four easy beats and all top-calibre players.
That had Wawrinka match-hardened and ready for Murray in the quarter finals and he completely dominated the match.
If the fact that Warwinka beat Murray wasn’t shocking enough, the fact that he won in straight-sets and dropped just nine games surely was as he scored the thumping 6-4, 6-3, 6-2 victory.
Murray couldn’t get his game going from the outset and finished with 15 winners opposed to 30 unforced errors while he won just 10-of-22 points at the net and a very low 54 per cent of points won on his first serve.
Wawrinka, meanwhile, had the game of his life set up by winning a massive 88 per cent of points on his first serve, 31-of-42 points at the net and hitting 45 winners to 37 unforced errors.
The victory for the 28-year-old Wawrinka continues what has been the best year on the ATP Tour of his career.
He already made the quarter-final of the French Open, just his third time he advanced that far in a major, the fourth round at the Australian Open and now by reaching the semi finals at Flushing Meadows, he is in the final four of a major for the first time in his career.
"I feel great and I'm really happy that's for sure. It's amazing to be in the semi-final in a Grand Slam for the first time especially after beating Andy Murray, the defending champion," Wawrinka said.
"To beat him in three sets the way I was playing today is quite good for me. Normally I can be a little bit nervous and I can lose a few games because of that, but today I was just focused on my game.
"My level of tennis right now is quite good and I'm really confident with myself, with my game on the court. I believe much more in myself now and my game is better too. I had some big confidence since the beginning of the year and that's helped me for sure."
While Wawrinka's win over Murray sees him advance to his first Grand Slam semi-final, world No. 1 Djokovic's 6-3, 6-2, 3-6, 6-0 win over Russian No. 21 seed Mikhail Youzhny sees him make his remarkable 14th straight major semi.
"It was never going to be an easy match against Mikhail, the quarter finals of a Grand Slam, and I was aware of his qualities and ability to come back in the match," Djokovic said.
"After I lost the third set I definitely tried to regroup and focus on every point individually and start playing the same game that I had in the first two sets. For some reason I allowed him to come back into the game and I started to push the ball, and being more passive allowing him to step into the court and come into the net.
"He was playing well, no question about it, and he was not making any mistakes. I started making a lot of unforced errors and the match turned around so it was important to get the early break in the fourth and after that I felt a big relief on the court and just went for my shots, and played great."
The semi-final between Wawrinka and Djokovic will now need the Swiss to pull out something special once again if he is to make the first Grand Slam final of his career.
He has beaten Djokovic twice before but those victories came way back in 2006 with the Serb winning the last 11 matches straight between the pair most recently in the fourth round of this year's Australian Open and also at last year's US Open.
Djokovic has certainly not forgotten his incredible battle with Wawrinka at this year's Australian Open that he eventually won 12 games to 10 in the fifth set in an amazing marathon that was heartbreaking for the Swiss.
Djokovic certainly expects something just as tough from a Wawrinka who has only gone from strength to strength throughout 2013.
"It's definitely one of the most exciting matches I have played in my life on this surface, against Stan. He played on a very, very high level in that match," Djokovic said.
"In the past we all knew that he has the quality to play that well, but not on a consistent basis. He has worked a lot on his movement and some variety of shots in his game, and he's a very complete player.
"He can play equally well on any surface and he has had one of the best seasons of his life. Today he won against the defending champion on Arthur Ashe, that was quite impressive and I'm sure he is very confident, and has nothing to lose. He's going to go for the win."
Neither of the men's semi finals will take place on Friday in New York with the focus on the two women's semi finals on Arthur Ashe Stadium.
First up is unseeded Italian veteran Flavia Pennetta taking on world No. 2 Belarusian Victoria Azarenka before world No. 1 Serena Williams takes on the fifth-seed from China Li Na.