NEW YORK — John Isner’s career fittingly ended with a final-set tiebreaker.

Isner put a volley into the net to end the match in his final singles tournament, falling in the second round of the U.S. Open to fellow American Michael Mmoh, 3-6, 4-6, 7-6 (3), 6-4, 7-6 (7).

“It’s tough. I like to think I work as hard as I can,” Isner told a Grandstand crowd that erupted in cheers as he trailed off into tears.

The 38-year-old Isner, who needed a wild card to get into the draw at Flushing Meadows, blasted 48 aces and won 86% of his first-serve points in a match that also included 63 unforced errors. Several times, the 6-foot-10 Isner fell to the ground while diving to make volleys.

Isner reached a career-best ranking of No. 8 in 2018, shortly after making it to the semifinals at Wimbledon. He won 16 singles titles and hit 14,470 aces, an ATP Tour record. That includes 113 in the longest match in tennis history, a first-round Wimbledon win against Nicolas Mahut in 2010 that lasted 11 hours, 5 minutes and ended at 70-68 in the fifth set.

Next up for the 89th-ranked Mmoh will be Jack Draper, who upset an apparently ailing Hubert Hurkacz, 6-2, 6-4, 7-5, extending his return to the tour after being out more than two months because of a shoulder injury.

Draper, a 21-year Brit who only came back to the tour in early August, showed no signs of injury with strong serves and groundstrokes, while Hurkacz appeared listless at times and called the courtside medics over during a changeover in the final set.

Hurcasz, the 17th seed from Poland, was coming off a semifinal showing at a tune-up event in Cincinnati in which he had a match point against No. 1 Carlos Alcaraz before eventually losing in three sets.

Sixth-seeded Jannik Sinner advanced with a 6-4, 6-2, 6-4 victory over fellow Italian Lorenzo Sonego.

Sinner has never lost to an Italian, improving to 10-0 against his countrymen. He’s seeking a deep run at Flushing Meadows after reaching the semifinals at Wimbledon this year and the quarterfinals at last year’s U.S. Open, losing to Alcaraz in a five-set marathon after holding a match point.

“I felt now my game has improved a little bit and developed,” said the 22-year-old Sinner, who won 89% of his first-serve points and was successful on 22 of 25 trips to the net. “Physically, I’m good and let’s see what’s coming.”

Alexander Zverev, the No. 12 seed, downed fellow German Daniel Altmaier 7-6 (1), 3-6, 6-4, 6-3. Zverev was among several players who noticed a scent of marijuana on the outer courts while playing in the first round, describing it as smelling like “Snoop Dogg’s living room.”

Zverev will face No. 19 seed Grigor Dimitrov, who downed Andy Murray in a convincing 6-3, 6-4, 6-1 victory in Arthur Ashe Stadium that included 45 unforced errors from the British three-time Grand Slam champion.

On the women’s side, second-seeded Aryna Sabalenka had little trouble with Jodie Burrage of Britain in a 6-2, 6-3 victory. Sabalenka advances to a third-round matchup against Clara Burel of France, who beat No. 25 Karolina Pliskova, 6-4, 6-2.

Ninth-seeded Wimbledon champion Marketa Vondrousova downed Martina Trevisan of Italy, 6-2, 6-2; American Madison Keys, the No. 17 seed, advanced with a 6-1, 6-2 victory over Yanina Wickmayer of Belgium; and No. 26 Elina Svitolina of Ukraine defeated Anastasia Pavlyuchenkova of Russia, 5-7, 6-4, 6-4.