Defending champion Carlos Alcaraz has cruised into the second round of the US Open after his opponent Dominik Koepfer retired with an injury during their primetime match at Arthur Ashe Stadium.

The 20-year-old top seed from Spain was leading 6-2 3-2 when Koepfer called it quits, having rolled his ankle at a grimace-inducing angle just minutes into the match.

Alcaraz will play Lloyd Harris in the second round at Flushing Meadows after the South African saw off Argentine Guido Pella 7-6 (7-5) 6-4 6-4.

"He's a great player, he has big shots so I have to be really focused on the match," Alcaraz said of his next opponent.

"Obviously (it) is going to be a tough one."

Any hope German Koepfer had of putting up a fight against Alcaraz evaporated after he stopped short along the baseline in the first game. He took a medical timeout to have his ankle taped and returned to the court with the score at deuce.

But he was clearly not at full strength and Alcaraz easily converted a break point with a well-placed drop shot.

Down a break in the second set, the world No.75 fended off a pair of break point chances in the fifth game before solemnly walking to the net to resign.

"Obviously I want to play battles. I want to play the full matches. This is not the best way to win a match," Alcaraz said.

"But obviously, playing the night session, I'm happy to come back early, have some rest. Well, a little bit more than I expect before starting the match.

"It's going to be better for me to recover into the next round."

Earlier on Tuesday, third-seeded Russian Daniil Medvedev steamrolled past Attila Balazs 6-1 6-1 6-0.

After losing to eventual champion Alcaraz in the Wimbledon semi-finals, Medvedev has had a quiet buildup to the season's final grand slam. He reached the quarter-finals of the Canadian Open and the round of 16 a week later in Cincinnati. But he has always produced some of his best work in New York, reaching the final in 2019, semi-finals in 2020 and winning it in 2021.

In round two he'll take on Chris O'Connell, who beat fellow Australian Max Purcell 6-4 6-3 3-6 7-6 (7-5).

Better news for compatriot Alex de Minaur, the 13th seed, who battled past Kazakhstan Timofey Skatov to claim a 6-2 3-6 6-1 7-5 victory.

Another two former champions punched their round-two tickets.

Switzerland's Stan Wawrinka scored a 7-6 (7-5) 6-2 6-4 win over Japan's Yoshihito Nishioka, while Andy Murray won his 200th grand slam match with a three-set victory over Corentin Moutet.

The two-time Wimbledon winner and victor here in 2012, overcame the Frenchman 6-2 7-5 6-3 to become the eighth male player in the Open era to reach the double-century.

"I hope it was entertaining, there were some fun points, so I'm happy to get through in straight sets," the 36-year-old Scot said.

"It was a long one but ... three hours is a lot shorter than some of my matches!"

Murray will meet Bulgarian 19th seed Grigor Dimitrov, who saved three match points in a 6-7 (9-11) 6-7 (5-7) 6-1 7-5 7-6 (11-9) triumph over Slovakia's Alex Molcan, in the second round.

Elsewhere, sixth-seeded Italian Jannik Sinner comfortably beat Germany's Yannick Hanfmann 6-3 6-1 6-1.

Russian Andrey Rublev, the eighth seed, advanced after defeating Frenchman Arthur Cazaux 6-4 7-6 (7-5) 6-1, but compatriot and 11th seed Karen Khachanov was upset by American Michael Mmoh 6-2 6-4 6-2.

German 12th seed Alexander Zverev had little trouble overwhelming Australian Aleksandar Vukic 6-4 6-4 6-4 and Poland's 17th seed Hubert Hurkacz overcame Swiss Marc-Andrea Huesler 4-6 5-7 7-6 (7-0) 6-3 6-1.

With PA.