The U.S. Open men's singles field was blown open on Friday when Alexei Popyrin upset defending champion Novak Djokovic 6-4, 6-4, 2-6, 6-4 in third-round action at New York.

The victory for Popyrin, a 25-year-old Australian who is seeded 28th, comes one day after U.S. Open favorite Carlos Alcaraz lost in the second round.

Djokovic, a 37-year-old Serbian who was seeded second, won his fourth U.S. Open title last year. Alcaraz captured the championship in 2022, and he arrived in New York having won the French Open and Wimbledon this summer.

At the Paris Olympics last month, Djokovic defeated Alcaraz in the gold-medal match.

Djokovic last lost a Grand Slam match before the fourth round at the 2017 Australian Open.

Djokovic committed 14 double faults, and Popyrin emerged with a 50-40 edge in winners.

"I spent a lot of energy winning the (Olympic) gold and I did arrive in New York not feeling fresh," Djokovic said. "I tried my best, I didn't have any physical issues. I just felt out of gas, and you could see that. From the first match, I just didn't find myself on this court.

"Life moves on. I'll try to recalibrate and look forward to what's next."

Meanwhile, Popyrin is headed to the fourth round of a Grand Slam event for the first time in his 23rd attempt.

"It's unbelievable because I've been in the third round about 15 times in my career, but I haven't been able to get past to the fourth round," Popyrin said. "To be able to do it against the greatest of all time to get into the fourth round is unbelievable. It's a great feeling and the hard work has paid off."

Next up for Popyrin is match against No. 20 Frances Tiafoe, who avenged his loss to No. 13 Ben Shelton in the 2023 U.S. Open quarterfinals, outlasting his fellow American 4-6, 7-5, 6-7 (5), 6-4, 6-3.

With the 4-hour, 6-minute win, the 26-year-old Tiafoe advanced to his fifth straight round of 16 at the U.S. Open, something no American man had done since Andre Agassi in 2005.

"I've got to say, Ben's an incredible player, man. He's an incredible player. He really is," Tiafoe said in a postmatch interview. "He goes for all kind of shots. He's got no care in the world. It's really annoying. ... He's really talented. He can come up with great shots. So can I. It's highlight after highlight. I hope you guys enjoyed the show."

After Shelton took the first set, he went ahead 5-4 but Tiafoe broke the 21-year-old's serve to take a 6-5 lead en route to winning the second set.

In a tight third set, Tiafoe staved off set point and forced a tiebreaker. Shelton grabbed a 6-0 lead, but Tiafoe held five straight set points, capitalizing on his opponent's errors. Shelton, however, recovered to close out the third set with a 143-mph serve.

Leading 5-4 in the fourth set, Tiafoe broke Shelton's serve to win the set 6-4, setting the stage for the decisive fifth set. Tiafoe took the early advantage by breaking Shelton for a 3-1 lead and eventually put it away on his second match point.

Shelton posted 63 winners to Tiafoe's 44 but committed 58 unforced errors compared to 27 for Tiafoe. Shelton finished with 23 aces to just five for Tiafoe, who saved 4 of 7 break points while his opponent saved 16 of 21.

In other action, No. 8 Casper Ruud of Norway escaped a two-set deficit to defeat China's Juncheng Shang 6-7 (1), 3-6, 6-0, 6-3, 6-1. Ruud had a 29-14 advantage in winners over the final three sets after Shang led 25-20 in that category through the first two sets.

Brandon Nakashima, a 23-year-old San Diego native, upset No. 18 Lorenzo Musetti of Italy 6-2, 3-6, 6-3, 7-6 (4) to match his best run at a Grand Slam event. Nakashima got to the fourth round at Wimbledon in 2022.

No. 12 seed Taylor Fritz cruised to a 6-3, 6-4, 6-2 victory over Argentine qualifier Francisco Comesana.

With the win, Fritz is the first American man since Agassi in 2003 to reach the round of 16 at all four majors in the same year. He next faces Ruud.

No. 6 seed Andrey Rublev of Russia and No. 9 seed Grigor Dimitrov of Bulgaria will face off in the round of 16 after straight-sets victories.

Rublev defeated No. 32 seed Jiri Lehecka of the Czech Republic 6-3, 7-5, 6-4, while Dimitrov eliminated Tallon Griekspoor of the Netherlands 6-3, 6-3, 6-1.

In the last match of the night, No. 4 Alexander Zverev of Germany advanced past Tomas Martin Etcheverry of Argentina 5-7, 7-5, 6-1, 6-3.

--Field Level Media