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

The 20-year-old top seed from Spain was leading 6-2, 3-2 when Koepfer retired, having rolled his ankle at a grimace-inducing angle minutes into the match. Alcaraz will play Lloyd Harris of South Africa in the second round.

"He's a great player, he has big shots so I have to be really focused on the match," said Alcaraz. "Obviously (it) is going to be a tough one."

Alcaraz drew a packed crowd to the iconic American stadium but the affair quickly unraveled as underdog Koepfer stopped short along the baseline in the first game, twisting his left ankle and losing much hope of putting up a fight.

He took a medical timeout to have his ankle taped and returned to the court with the score at deuce but was clearly not at full strength and Alcaraz easily converted a break point with a well-placed drop shot.

The German showed grit as he fended off a break point in the third game of the first set but was overheard telling his team that his ankle was in terrible shape, as his camp questioned whether he should continue.

Koepfer buried his head in his towel after Alcaraz forced him into a forehand error to convert on a break point chance in the seventh game.

Wimbledon champion Alcaraz was in fine form, sending over 19 winners with few mistakes across the match, and broke Koepfer to love in the third game of the second set after the German whacked a backhand shot out of bounds.

Koepfer fended off a pair of break point chances in the fifth game before solemnly walking to the net to resign.

"Obviously I have to give credit to him," Alcaraz said in on-court remarks after the match. "First step on the court, I felt great... the same energy that I felt last year."

Alcaraz will lose his world No 1 spot when the tournament wraps after rival Novak Djokovic demolished Frenchman Alexandre Muller in his opening match on Monday, a result that meant the Serb will replace him at the top of the rankings.