Defending champion Novak Djokovic followed Carlos Alcaraz out of the door at the US Open as he suffered a shock defeat by Alexei Popyrin in the third round.

Australia’s 28th seed Popyrin stood with his arms aloft as he wrapped up a surprise 6-4 6-4 2-6 6-4 win to hand Djokovic his earliest US Open exit in 18 years.

The Serb will end the year without winning a Grand Slam for the first time since 2017, while his search for a record 25th major title goes on.

Djokovic, 37, was far from his clinical best, serving a career-high 14 double faults in a Grand Slam match and committing 49 unforced errors.

His exit follows that of French Open and Wimbledon winner Alcaraz, who lost to unseeded Dutchman Botic van de Zandschulp in the second round.

Popyrin, 25, will make his first fourth-round appearance at a Grand Slam when he faces Frances Tiafoe, who moved past fellow American Ben Shelton in a five-set thriller.

“It’s unbelievable because I’ve been in the third round about 15 times in my career but haven’t been able to get to the fourth round,” Popyrin said.

“To be able to do it against ‘the Goat’ [greatest of all time] to get into the fourth round is unbelievable, it’s a great feeling that the hard work has paid off.”

Popyrin enjoyed a positive build-up to the US Open, claiming his maiden ATP Masters 1000 title in Montreal earlier this month.

The Sydney-born player was brimming with confidence as he manoeuvred his way through the first set, fending off five break points before striking at 4-4 and serving it out.

He looked even better in the second, steadily going about his work and winning 88% of points on his first serve as Djokovic continued to falter.

The 24-time major winner finally burst to life at the beginning of the third set, winning the first three games before a blip allowed Popyrin to break back.

But Djokovic was quick to respond and animatedly demanded more noise from the lively crowd on Arthur Ashe Stadium as he restored his advantage and broke for a third time to keep his title defence alive.

Djokovic was aiming to win a fifth US Open that would have moved him past Margaret Court and take sole ownership of the all-time record for the most Grand Slam singles titles.

The pair continued to go toe-to-toe in set four, but Popyrin landed Djokovic in deep trouble when he he successfully converted his fourth break point in the fifth game.

He held firm in his next service game, too, saving two break points before a series of double faults and careless errors from the usually clinical Djokovic moved the 28th seed to the brink of a seismic victory.

With a double break behind him, Popyrin failed on his first attempt at serving out the match but he was more successful the second time around, landing three huge serves before Djokovic pushed the first match point long.

Earlier, Tiafoe avenged his defeat by Shelton at last year’s US Open by beating the 13th seed in an all-American five-set thriller.

The pair, who are good friends, faced each other in the quarter-finals in New York last year with Shelton emerging as the victor.

But it was the lower-ranked Tiafoe who won on Friday, coming from behind twice to triumph 4-6 7-5 6-7 (5-7) 6-4 6-3 after more than four entertaining hours on Arthur Ashe Stadium.

“Ben is an incredible player, he really is. He goes for all kinds of shots, he’s got no care in the world. It’s really annoying,” 20th seed Tiafoe said.

Meanwhile, American 12th seed Taylor Fritz continued his perfect run in New York with a 6-3 6-4 6-2 victory against Argentina’s Francisco Comesana.

Fritz, who has yet to drop a set, will face Norway’s Casper Ruud, a finalist in 2022 who made a remarkable comeback from two sets down to beat Shang Juncheng of China 6-7 (1-7) 3-6 6-0 6-3 6-1.

Russian sixth seed Andrey Rublev was the first men’s singles player to make it into the fourth round with an assured 6-3 7-5 6-4 victory over Czech Jiri Lehecka.

Rublev, a 10-time Grand Slam quarter-finalist who has yet to win a major, will face Grigor Dimitrov after the Bulgarian ninth seed claimed a dominant 6-3 6-3 6-1 win against Dutchman Tallon Griekspoor.