The Aussie men's No.2 never looked like grasping the opportunity to earn his first grand slam quarter-final date as he succumbed 6-3 6-3 6-3 on Court Suzanne Lenglen in a bloodless fourth-round clash on Sunday.
Outplayed by the world No.12 in all departments, it was a huge let down for 25th seed Popyrin who had been hoping to go at least one round further than last year's US Open when he had downed Novak Djokovic before falling in the last-16 to Frances Tiafoe.
The Sydneysider's exit in nine minutes under two hours meant that only Daria Kasatkina, in her first slam since gaining permanent residency, is now the last Australian standing, as she faces Russian teenage sensation Mirra Andreeva in Monday's last-16 clash.
Popyrin had harboured such high hopes going into the match after not dropping a set in his first three contests, and all started swimmingly as he broke the 28-year-old Paul in the opening game.
Alas, that was as good as it got for Popyrin.
The American, renowned for his toughness, saved the rest of the 10 break points he faced throughout, never allowing the Australian to get a foothold, while 37 unforced errors told of 'Poppy's' underwhelming day.
Paul had battled through two consecutive five-setters to reach this stage but could hardly credit that Popyrin, a powerhouse he felt had the power to take the racquet out of his hands, should give him no trouble at all.
"I am very glad (about) a straight-sets win. I have been playing some long matches, so that one felt really good," said Paul, who had spent more than three-and-a-half hours more on court than his opponent.
"My team has been doing a great job getting ready for each match but definitely shorter matches like this help a lot."
Paul's toughness was evident when Popyrin had two break points at 3-3 which the American repelled in the opening set before cashing in on a Popyrin double fault for a 5-3 lead.
Serving for the set, Paul found himself for once on the back foot as Popyrin earned three break-back points.
But the 12th seed showed huge resolve to fight back and seal the set in 42 minutes.
At the start of the second, a horrendous missed forehand sitter from Popyrin handed Paul an immediate break and the sad-eyed exchanges with his box demonstrated only the Australian's frustration.
He has been lamenting all season his inability to find a consistency of performance and, again, this display was nowhere near the standard he had displayed in beating Portuguese Nuno Borges in the previous round.
Popyrin's forehand, so reliable against Borges, began to malfunction alarmingly as he was again broken for Paul to race to a two-set lead.
Any chance of a comeback was soon extinguished when Paul, for a third set running, struck with an early break, and Popyrin cut a forlorn figure by the time a 26th Paul winner flashed by him on the final point.
Paul, the first American man in the quarter-finals here since Andre Agassi in 2003, is looking in good nick, and will need to be when he plays either compatriot Ben Shelton or the reigning champion Carlos Alcaraz in the quarters.
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