Andy Murray's US Open hopes went up in smoke as big-serving South African Kevin Anderson stunned the world number three with a thrilling four-set victory.
Murray had won five out of six previous meetings with Anderson but the 15th seed played the match of his life in Louis Armstrong Stadium to win 7-6 (7/5) 6-3 6-7 (2/7) 7-6 (7/0).
It is the first time in 19 major tournaments that Murray has failed to make the quarter-finals, where Anderson will now play fifth seed Stan Wawrinka.
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Anderson had thrown away a two-set lead against Novak Djokovic at Wimbledon in July but he showed few signs of nerves this time as he sailed into his first grand slam quarter-final.
"I played one of the best matches of my life and to get through to the quarter-finals feels just amazing," Anderson said.
"It's not easy playing Andy, I felt he was right in it. He's such a fighter, such an amazing player. I tried my best to stick with it."
Murray had New York City's Frank Lampard in his support box, but the British number one has rarely felt the love on Armstrong, where he was defeated by Stan Wawrinka in 2010 before enduring struggles against Marin Cilic in 2012 and Robin Haase last year.
Anderson hit a 132mph ace, one of 25 in the match, with his very first effort and that established the tone as both players struggled to trouble the other's serve in the first set.
Murray led 2-1 in the tie-break, with the mini-break, but as he began a second serve a spectator rose to his feet, prompting the umpire to halt the Scot's action.
It was enough of a diversion for Murray to double fault and when Anderson was given the chance to serve out at 5-4, he pounced, first with a strong serve and then a thumping forehand winner to clinch the first set.
Murray was rattled and carried his frustration into the second as a double fault helped Anderson storm into a 4-1 lead, with the Briton sending what appeared to be ironic fist-pumps towards his box.
Anderson had been expected to outpower Murray, but he was now outplaying him too, with one point seeing the South African chase down a drop-shot before cutting a crafty winner down the line.
Down 5-1 and two breaks, Murray showed glimpses of a fightback, breaking once, and then earning a point at 5-3 to do so again, but a nervy Anderson found a timely ace to crawl over the line.
The South African took a six-minute toilet break before the third, which irritated Murray, who pointedly asked the umpire what constituted a "reasonable amount of time" to be off.
Despite falling behind, it was Murray who had finished the second set on top but the delay again diverted the Briton, who conceded another break at the start of the third.
Seething, Murray broke back to win three games in a row while taking inspiration from a handful of fired-up fans nearby, but the Scot let his emotion get the better of him and instantly handed back the break.
Swiftly destroying his racket, which he then handed to his new-found friends, order was restored with both players holding on for another tie-break.
This time, however, the wind blew in Murray's favour as a lucky net-chord and then a booming serve sealed the set to spark hopes of a comeback.
Murray settled down in the fourth but so did Anderson, who could have broken in the fourth game but slapped a short forehand into the net.
Serves dominated again for the rest of the set, until the tie-break, where Murray crumbled as Anderson hit a blistering forehand return en route to a 6-0 lead.
Murray's end was quick as Anderson converted at the first time of asking with another emphatic return which sealed a momentous victory in four hours and 18 minutes.