De Minaur wore down veteran British marathon man Dan Evans 6-3 6-7 (4-7) 6-0 6-0 to clinch a last-16 berth for a fifth consecutive slam after the seed-slaying Thompson claimed yet another big scalp on day six in New York.
After sending world No.7 Hubert Hurkacz packing in round two, Thompson took out 30th seed Matteo Arnaldi 7-5 6-2 7-6 (7-5) to storm into the fourth round at Flushing Meadows for a second time.
Thompson promptly branded the high-stakes match-up with his Sydney mate "unreal".
"For sure an Aussie in the quarters. I hope that it is me," he beamed.
Jordan Thompson reckons he's in the form of his life. (AP PHOTO)
With Alexei Popyrin basking in the glory of his stunning defeat of defending champion Novak Djokovic, Australia has converted its biggest US Open contingent in 43 years into three players in the men's last 16 for the first time this century.
And after shifting up a couple of gears to produce his most impressive tennis of the tournament, de Minaur suddenly looks like a man on a mission again.
Playing his first singles event since withdrawing from Wimbledon with a hip injury, de Minaur felt he was only functioning at 85 per cent of his physical capacity in the first two rounds.
But the world No.10's movement was lightning in a quality contest with Evans, who has made a habit of knocking out Australians in New York.
De Minaur, though, avoided enduring the same Flushing Meadows fate as Bernard Tomic, James Duckworth and Popyrin three years ago.
He ran Evans ragged on Louis Armstrong Stadium, four days after the 34-year-old featured in a five-hour, 35-minute epic, the longest US Open match in history, with Karen Khachanov.
Alex de Minaur's movement was sharp as he ousted Dan Evans. (AP PHOTO)
Thompson will take a power of stopping, though, when the Australians collide on Monday (Tuesday AEST).
Also playing the tennis of his life, having won his maiden ATP title this year in Los Cabos and made the final in Atlanta, the proud Paris Olympian has now matched his career-best grand slam run from the 2020 US Open.
Yet to drop a set this campaign, Thompson fell behind 4-2 in the third against Arnaldi, a 2023 Italian Davis Cup winner widely considered one of the brightest young stars in tennis.
But, as he does, Thompson went straight back to work, breaking Arnaldi in the seventh game and recovering from 3-0 down in the third-set tiebreaker to seal victory after two hours, 33 minutes.
"It was a great match from me. The third round is pressure. I have not been there too much in my career," he said.
"I was getting a little bit agitated there but I dealt with it really well and came out on top. It is really pleasing to win under lights in New York on a Saturday night."
The 30-year-old is set to claim a new career-high ranking inside the world's top 30 and believes he is only now starting to peak.
"It is hard to argue with. I feel like I am getting better as I get older," Thompson said.
"It is definitely the best I have been playing in my career and my results and ranking dictate that."
Chris O'Connell (pic) hailed Jannik Sinner the best he's ever played after losing to the world No.1. (AP PHOTO)
But Chris O'Connell's Open is over after Australia's fourth third-round representative copped a lesson from world No.1 Jannik Sinner on Arthur Ashe Stadium.
"The best tennis player I've ever played, for sure," O'Connell said after exiting with a 6-1 6-4 6-2 loss.
O'Connell can console himself with a career-best payday of $US215,000 ($A315,000) for reaching the last 32.
Popyrin, the 28th seed, meets world No.20 Frances Tiafoe in the fourth round on Sunday night (9am Monday AEST) in a prime-time showdown.