Australia's big last hope floundered in a sea of forehand errors to succumb 6-3 7-5 6-2 to inspired Englishman Jack Draper on Wednesday (Thursday AEST).
De Minaur had been fancied to reach his maiden grand slam semi-final against the lower-ranked Draper, especially having beaten the 22-year-old in all three previous encounters.
Britain's Jack Draper returns during his straight-sets defeat of Alex de Minaur in New York. (AP PHOTO)
But, looking bothered by the hip injury that had sidelined him sim Wimbledon, the world No.10 struggled to find top gear at Arthur Ashe Stadium as Draper continued his own march through the Open draw.
The free-hitting left-hander has yet to drop a set all tournament and has conceded a meagre 36 games in 15 sets on the way to becoming the first British man to reach the last four at Flushing Meadows since former world No.1 Andy Murray won the title in 2012.
"It's amazing. On the biggest court in the world, it's a dream come true for me," Draper said.
"I played a solid match and I feel the best fitness-wise that I've felt in a long time.
"That's where Alex has got me in the past. I also think he was struggling a little bit today with something and that helped me a little bit.
Alex de Minaur and Jack Draper embrace at the net after the Briton's quarter-final victory. (AP PHOTO)
"But credit to Alex, he's an unbelievable player and fighter, and we're going to have many more battles to come."
Draper's run is eerily similar to that of another English success story when Emma Raducanu shocked the tennis world by winning the women's crown without conceding a set in 2021 as a qualifier.
Draper winning two more matches and lifting the title would not be quite as surprising, but the emerging star's incredible run thus far looks that of a man on a similar journey to Raducanu.
It was unclear exactly how hindered de Minaur was.
He clutched at the leg on occasions while trying to transition in points.
Other times, he flew around centre court with signature lightning speed.
Regardless, Draper delivered a masterclass to end Australia's singles interest in the final grand slam of the year.
While de Minaur's horror unforced error count grew the classy Brit dictated from the get-go with powerful groundstrokes, big serving and a succession of sumptuous forehand drop shots.
Draper's reward is a first grand slam semi-final appearance on Friday against either world No.1 and reigning Australian Open champion Jannik Sinner or fifth-seeded 2021 US Open winner Daniil Medvedev.
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