Novak Djokovic followed Carlos Alcaraz in crashing out of the US Open after Australian Alexei Popyrin pulled off the second major shock in two nights.

Alcaraz was the subject of one of the tournament’s biggest upsets when he was dumped out by world number 76 Botic van De Zandschulp on Thursday night.

And 24 hours later, defending champion Djokovic joined him in leaving New York early after the 28th seed won 6-4 6-4 2-6 6-4.

Defeat for Djokovic means it is the first time since 2017 he has not won a grand slam title and is his earliest exit at a major since the Australian Open that year.

It extends the Serbian’s wait for a record-breaking 25th grand slam title and, at 37, Djokovic’s domination may be coming to an end.

He came into the tournament at Flushing Meadows knowing he would be up against it owing to his emotionally draining Olympic win and being without a hard-court match since March.

But even he probably did not expect to struggle to the extent he did, with 13 double faults – a career high in a grand slam match – typifying the challenges he faced.

It is perhaps no surprise that all three players who finished on the podium in Paris have lost early in New York, Alcaraz and bronze medallist Lorenzo Musetti also heading out.

For Popyrin this was the win of his career and third time lucky against Djokovic, having lost at the Australian Open and Wimbledon.

There was also a nice bit of symmetry about his victory as it inflicted Djokovic’s earliest US Open defeat since 2007 when he lost to Lleyton Hewitt, who was sat in Popyrin’s box.

He meets Frances Tiafoe in the next round and everyone left in the men’s draw will now see this as their best chance to win a grand slam.

Tiafoe, seeded 20th, beat his good friend Ben Shelton 4-6 7-5 6-7 (3) 6-4 6-3 to become the latest home player to advance.

Tiafoe said: “I’ve got to say Ben is an incredible player man, he really is. He goes for all kind of shots, it’s really annoying.

“We both move really well. It is highlight after highlight. Four hours, it was a battle.”

Eighth seed Casper Ruud came from two sets down to beat Shang Juncheng, winning 18 of the last 22 games.