De Minaur put friendship to the side to end Thompson's spirited campaign with a hard-earned 6-0 3-6 6-3 7-5 victory and become the first Australian since Lleyton Hewitt 20 years ago to reach three consecutive grand slam quarter-finals.
His stocks rising with every win, the 10th seed will next face English world No.25 Jack Draper on Wednesday (Thursday AEST) in an Ashes-like battle for a coveted place in the last four.
After arriving in New York under a fitness cloud and with "low expectations", de Minaur has regained belief and form to move quietly into title reckoning.
Moving freely and showing no signs of the hip injury that shattered his Wimbledon and Olympic dreams, de Minaur showed his childhood friend and Davis Cup teammate little mercy on Monday.
Thompson fought tooth and nail and threatened to drag the match in to a deciding set before de Minaur's class and relentlessness ultimately prevailed.
Thompson was reduced to bouncing his racquet into the court in frustration while suffering the ignominy of a first-set bagel.
Jordan Thompson loses his cool during his four-set loss to compatriot Alex de Minaur. (AP PHOTO)
And even after Thompson finally won a game, then broke from 40-0 down to snatch the second set, there was no let-up from de Minaur as he went swiftly back to work on Labor Day in America.
The French, Wimbledon and now US Open quarter-finalist regained the ascendancy to claim a two-sets-to-one lead, and there was more racquet smashing and berating his box from Thompson as he sensed the match slipping away.
With one last stand, Thompson broke early in the fourth set to raise hopes of a famous underdog comeback.
But there was nothing friendly about de Minaur immediately striking back before finally subduing Thompson after a seesawing four-break fourth set to take victory after two hours 57 minutes.
For all the first-week heroics of Thompson and Novak Djokovic slayer Alexei Popyrin, de Minaur is once again Australia's last man standing at the season's final major.
The standardbearer's feat of making three consecutive grand slam quarters is one that eluded even former world No.1 Ash Barty and former women's US Open champion Samantha Stosur during distinguished careers.
No Australian has managed it since Hewitt in 2004-05.
The dual major winner followed up forays to the last eight at Roland Garros and Wimbledon with charges to successive finals at Flushing Meadows and Melbourne Park.
Alex de Minaur hits a forehand during his clash with fellow Sydneysider Jordan Thompson. (AP PHOTO)
After also becoming the first Australian since Hewitt two decades ago to make the second week of all four majors in a calendar year, de Minaur will now be hoping to further emulate his Davis Cup captain's 2004 accomplishment by going all the way to the final on Sunday.
He has a golden opportunity, with de Minaur having won all three previous encounters with Draper, including the past two on hard courts.
If he can continue his march through the draw, de Minaur will meet either world No.1 Jannik Sinner, 2021 US Open champion Daniil Medvedev or 14th seed Tommy Paul in his maiden grand slam semi-final.
While it's the end of the road for Thompson, the 30-year-old will leave the Big Apple with a half-a-million-dollar payday and a career-high ranking of No.29 in the world to be on course for a first-time grand slam seeding at the Australian Open in January.
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