The ninth-seeded Thiem beat Anderson for the first time on hard courts, 7-5, 6-2, 7-6, to make his first Grand Slam quarterfinal outside of Roland-Garros.
Thiem had never passed the fourth round in Flushing, falling three times in the past four years. But the 24-year-old Austrian served nearly perfectly, took advantage of his first time in the new, spacious Louis Armstrong Stadium and gave the 6-foot-8-inch South African little time to unleash his mammoth groundstrokes.
“It was one of my best matches ever,” Thiem said.
Anderson won the first six of their head-to-head meetings, all on hard courts. But Thiem won in straight sets, earlier this year, on the quick-moving clay in Madrid.
On Sunday, he played as if they were on a clay court at times and flipped the script against Anderson. Thiem, not Anderson, dominated on serve, winning 91 percent of his first-serve points (41/45) and never facing a break point. His heavy groundstrokes and soft drop shots forced Anderson to retrieve from side-to-side, back-to-front.
"I served really, really well today," Thiem said.
Anderson served and volleyed, and he came to net 48 times, trying to take advantage of Thiem's deep return position – he stood nearly next to the line judges and with his back against the Chase sign in Louis Armstrong Stadium.
But the fifth-seeded South African might have been feeling the effects of his earlier matches. He had already spent nearly 10 hours on-court, battling cramps and beating Ryan Harrison in five sets during his opener, and on Friday, playing another three hours, 43 minutes against No. 28 seed Denis Shapovalov.
"I could change my return position, and this helped me a lot. And also the court, I think, made a big difference. It's a huge court. I could go very far back like I do on clay usually," Thiem said.
He broke in the 11th game of the opener, for the first break of the match and served out the set. Anderson was then broken to love to start the second and Thiem rolled from there.
After the second set, the South African went to the locker room for more than eight minutes, and he regrouped to erase a break point in the seventh game and force a tiebreaker. But Thiem, on his first match point, chased down an Anderson volley for a backhand slice winner, his 41st of the day.
"He had some unbelievable passing shots, made me hit another ball," Anderson said. "That made things pretty tough."
WHAT IT MEANS: Clay-court specialist? Not Dominic Thiem, not this fortnight. Eight of Thiem's 10 ATP titles have come on the red dirt, and before Sunday, the Austrian had reached three Grand Slam quarterfinals, all at Roland-Garros (2016 SF, 2017 SF, 2018 final), and he was 0-6 in Grand Slam fourth-round matches outside of Paris.
But the right-hander, who turns 25 on Monday, had a clear game plan for the Flushing courts and executed it well to end Anderson's hopes of returning to the US Open final. Thiem managed to put behind him his near miss of a year ago, when he led Juan Martin del Potro two sets to zero, and had two match points before falling in five sets.
"I was pretty close last year. It was very painful," Thiem said. "So I'm happy that I made it, and it was an amazing victory over one of the best players right now. Also first time quarterfinals outside Paris, but most of all, I'm happy with the performance."