Querrey, 29, won 3-6 6-4 6-7 (4-7) 6-1 6-1 to become the first American to reach a Grand Slam semi-final since Andy Roddick at Wimbledon in 2009.
The Briton, 30, led by a set and a break but lost 12 of the last 14 games as he appeared to struggle physically.
The defeat means Novak Djokovic could overtake Murray as world number one.
Second seed Djokovic, who plays Tomas Berdych later on Wednesday, needs to win the title to return to the top of the rankings.
Murray looked on course for an eighth win in nine matches against Querrey when he led by a set and a break, but less than two hours later he was out, after the American fired down his 27th ace.
Querrey took his chance superbly, hitting 70 winners, 30 of them from the net as he attacked at every opportunity.
For Murray, it appeared that the hip injury that disrupted his build-up to Wimbledon had finally caught up with him.
After breaking serve to lead 4-3 in the second set, letting out a loud "come on!", Murray dropped serve twice in a row, his opponent firing a brilliant backhand to clinch the set.
Any thought that it was a momentary lapse from the champion disappeared when Murray was broken again serving for the third set, but he took the tie-break on his fourth set point and seemingly regained control.
In fact, it was Querrey who took command as Murray appeared underpowered and unable to move freely.
The Scot won just nine points on serve in each of the fourth and fifth sets, with an average serve speed down at just 108mph, allowing Querrey to tee off on the return.
The American played a magnificent point at the net to break for the eighth time, serving out the match after two hours and 41 minutes.
source:tori news
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