NEW YORK — World No. 1 Novak Djokovic advanced into the third round of the U.S. Open in New York without stepping onto the court Wednesday, and No. 5-seeded Milos Raonic of Canada became the tournament’s first significant upset victim as he lost to American Ryan Harrison.

The Czech Republic’s Jiri Vesely withdrew from his scheduled second-round match against Djokovic because of left forearm inflammation. The left-handed Vesely hurt his arm in Winston-Salem, North Carolina, last week and had to retire from his final match before the U.S. Open.

Vesely beat the Serbian star 6-4, 2-6, 6-4 on clay in Monte Carlo in April.

Later Wednesday, Harrison, who is ranked No. 120, stunned Raonic, this year’s Wimbledon runner-up, by a score of 6-7 (4), 7-5, 7-5, 6-1.

Harrison double-faulted on set point to give Raonic the opening-set tiebreaker, but the American rallied to take the second set, winning it on his seventh set-point opportunity.

Raonic used a medical timeout early in the third set to have his left wrist examined, and he could not stay with Harrison thereafter. Harrison, 24, recorded service breaks in the fourth and sixth games of the fourth set and served out the match at love to complete a victory that took three hours, 37 minutes. He finished with 48 winners to 38 unforced errors.

“It’s mental maturity, a little bit of stabilization with everything around me that is allowing me to play with a sense of calm and also with excitement,” Harrison said. “My personality is a very fiery one. I like to be really intense when I’m competing. Flirt with that line of getting so intense that it’s taking me away from what I was trying to accomplish out there.”

Raonic said he was slowed by cramping that started halfway through the second set.

Raonic’s biggest weapon is his serve, but it did not make a major impact against Harrison.

“That’s normally my go-to,” Raonic said. “That can keep me out of situations. I think that sort of added a little bit more than I normally have to deal with. I think that just sort of caught up to me throughout that match.”

Two seeded American men also won second-round matches.

No. 20 seed John Isner got by Belgium’s Steve Darcis 6-3, 6-4, 6-7 (10), 6-3, and 26th-seeded Jack Sock breezed past Germany’s Mischa Zverev 6-1, 6-1, 6-2.

Also, two Frenchmen reached the third round as 10th-seeded Gael Monfils advanced to with a 7-5, 6-4, 6-3 victory over the Czech Republic’s Jan Satral, and ninth-seeded Jo-Wilfried Tsonga got past Australia’s James Duckworth 6-4, 3-6, 6-3, 6-4.

Seventh-seeded Marin Cilic eliminated Ukraine’s Sergiy Stakhovsky 6-1, 6-2, 6-3.

In women’s action, former world No. 1 Caroline Wozniacki, one point from falling behind 5-0 in the opening set, rallied to upset ninth-seeded Russian Svetlana Kuznetsova in straight sets.

The unseeded Dane, slowed by injuries this season, took advantage of some sloppy play by the former U.S. Open champion to post a 6-4, 6-4 victory and advance to the third round.

Next up for Wozniacki is Romanian Monica Niculescu, a 6-0 6-1 winner against compatriot Ana Bogdan.

Second seed Angelique Kerber stayed on track in her quest to unseat Serena Williams as world No. 1 by beating Mirjana Lucic-Baroni of Croatia 6-2, 7-6 (7) to reach the third round.

Australian Open winner Kerber rifled home an ace to finish the first set against the free-swinging, 34-year-old Lucic-Baroni, then won a seesaw second set in which each player was broken three times on the way to a tiebreaker.

The Croat held two set points during the decider, and three overall, before losing it 9-7.

British 13th seed Johanna Konta felt “embarrassed” after recovering from a health scare at a humid U.S. Open on Wednesday to claim her place in the third round with a 6-2, 5-7, 6-2 win over Bulgaria’s Tsvetana Pironkova.

Konta was leading by a set but serving at set-point down in the second when she suddenly dropped to her knees, shaking and struggling to catch her breath as temperatures neared 88 degrees.

After receiving extensive treatment, including ice bags, first from the umpire and later from a doctor, Konta dropped the set on a double fault.

But after a bathroom break between sets, the 25-year-old recovered in time to set up a third-round clash with Belinda Bencic of Switzerland.

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