South African 15th seed Kevin Anderson stunned British third seed Murray 7-6 (7/5), 6-3, 6-7 (2/7), 7-6 (7/0) to end his run of 18 consecutive major quarter-finals since the 2010 US Open.
"That's something that is disappointing to lose because of that. That's many years' work that's gone into building that sort of consistency. To lose that is tough," said Murray on Monday.
"Also to lose a match like that, that was over four hours, tough after a couple of tough matches earlier in the tournament as well, it's a hard one to lose, for sure."
"It was the match of my life," Anderson said. "This is a great accomplishment for me."
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Anderson, who won his third career title two weeks ago at Winston-Salem, is the first South African in New York's last-eight since Wayne Ferreira in 1992.
"I'm just so excited to be through," said Anderson. "Beating a guy like Andy, I really feel like I've taken a step forward. It's amazing. I feel like it's a great accomplishment."
Anderson, 1-5 in prior matches against Murray, fired 25 aces in ending an 0-15 career hoodoo against top-10 opponents to book a last-eight date with Swiss fifth seed Stan Wawrinka.
The Swiss dropped his first set of the tournament but reached an eighth quarter-final in his past nine Grand Slams, denying 68th-ranked Young his first Slam quarter-final.
With New York City FC and former England midfielder Frank Lampard watching from the player's box, Murray fell behind two sets and a break, roared back, but ultimately could not win the tension-packed encounter at Louis Armstrong Stadium.
Murray, the 2012 champion, had 49 winners and 20 unforced errors, but did not make a forehand winner until the last game of the second set. Anderson blasted 81 winners to 57 unforced errors.
"Of course Roger will be the favorite of the match but I will have nothing to lose," said Gasquet.