He could only applaud as former world No.10 Tiafoe, now a triple quarter-finalist at his home slam, crunched a forehand winner to clinch victory before the pair embraced at the net.
Tiafoe will next face Bulgarian ninth seed Grigor Dimitrov, who earlier outlasted sixth-seeded Russian Andrey Rublev 6-3, 7-6 (7-3), 1-6, 3-6, 6-3.
The other locked-in men’s quarter-final will pit German fourth seed Alex Zverev against American No.12 seed Taylor Fritz, who came from two sets down to upset Zverev in the fourth round at Wimbledon in July.
Double faults first became a problem as Popyrin – a Roland-Garros junior champion in 2017 who was born in Sydney to Russian parents – tried to serve out the second set and level a riveting slugfest.
The 25-year-old had weathered the storm coming from the other end of the court and held triple set point to level their round-of-16 showdown at a set apiece.
That is where it unravelled for Popyrin, weeks separated from a career-best Masters 1000 triumph in Montreal and two days after dethroning defending champion Novak Djokovic.
Back-to-back errors followed, before Tiafoe nailed a down-the-line backhand return winner to enliven an Arthur Ashe Stadium crowd baying for their countryman.
Two points later, the Australian double-faulted off the net to change the course of both players’ fortnight. Fast-forward to the second-set tiebreak, and two more double faults helped put him in a two-set hole.
It was particularly galling, given Popyrin also held consecutive break points in the fourth game of the match, at a time his Dunlop axe was causing all sorts of wounds to Tiafoe.
The man known as “Big Foe” made his momentum swings count more often, leaving Popyrin with the titanic challenge of chasing the United States hero down in front of his home crowd.
The third set was surprisingly uncompetitive from Tiafoe, who twice dropped serve and barely escaped another time in between, giving Popyrin hope of doing the unthinkable.
That set the stage for an absorbing fourth set, where both players again had their chances.
Tiafoe had lost 15 of the previous 20 points by the time he collapsed to 0-30 in the third game of the set. Popyrin barely missed a scorching backhand return on the ensuing point, but the next one summed up his night.
Having worked his way on top in the point, Popyrin opted for an ill-advised drop shot that was not only the wrong choice but poorly executed, presenting Tiafoe ample time to chase it down and put a forehand away.
The American held two points later, shutting the door on another Popyrin opportunity.
Serving at 2-3, Popyrin double-faulted for 0-30, then did so again on the second break point he faced in the game to fall behind for good despite his last-gasp attempt to extend the match.
Popyrin finished with 24 aces and 55 winners to Tiafoe’s 14 and 44, but also nine double faults to his conqueror’s one. In a match of small margins, that was one of the key differences.
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Popyrin slipped to No.63 in the world while prioritising playing at the Paris Olympics, where he impressed in reaching the last 16, before storming into the top 25 for the first time with a giant-killing Montreal run that ended with five consecutive top-20 scalps, including two over top-10 opponents.
He will return to an equal-career-high ranking of No.23 next week as reward for an outstanding American hardcourt swing that sets him up to be a serious threat at the 2025 Australian Open. Popyrin insists he has not thought about the Australian summer yet, but leaves the US with soaring confidence and an ambition to help his country go one better in the Davis Cup after reaching the past two finals.
“If you told me at the start of the summer that I would have been 23 in the world, with a Masters title and [making the] second week of a slam for the first time, I probably would have taken it, considering the position I was in,” Popyrin said.
“If I hadn’t won a match in Montreal or Cinci, I probably would have dropped outside 90 in the world. So, considering all that, I think it was a very successful summer.
“[But] it definitely does feel like a little opportunity lost. I think this match was changed by, I think, one, two or three points. He won three more points than I did all match, and he won three sets, so that just shows you how close it was.”
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