Djokovic, the world number one and defending champion, was tested in his first-round match against Poland’s Jerzy Janowicz on Monday.
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Djokovic will face 51st-ranked Guido Pella or No. 61 Mikhail Youzhny in the third round Friday.
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“I’m very, very disappointed right now”, said 23-year-old Vesely.
In the women’s event, second seeded Angelique Kerber, the Australian Open champion, needed just 33 minutes to progress but Roland Garros victor Garbine Muguruza required three sets and a visit from the doctor before she survived. The left-handed Vesely hurt his arm in Winston-Salem (N.C.) last week and had to retire from his final match before the U.S. Open.
Kvitova, the 14th seeded Czech who recorded her best performance in NY 12 months ago when she made the last-eight, beat Turkey’s Cagla Buyukakcay 7-6 (7/2), 6-3.
Playing an opponent also coming off a five-set match, American John Isner advanced in four sets in the second round of the U.S. Open.
Vesely is only one of five players to beat Djokovic this year when he won their match during April on clay in Monte Carlo.
The fifth-seeded Raonic was treated by a trainer for problems with his left wrist and left thigh during Wednesday’s match and generally looked tired as play went on. And in his first-round U.S. Open victory over Jerzy Janowicz, Djokovic received treatment on his right arm and served much slower.
The 13th-seeded Konta advanced to the third round at the U.S. Open with a 6-2, 5-7, 6-2 victory in 2 hours, 33 minutes over Tsvetana Pironkova on Wednesday.
In other action, two-time U.S. Open runner-up Caroline Wozniacki beat a top-10 opponent for the first time in almost a year, turning things around after dropping the first four games and eliminating 2004 U.S. Open champion champ Svetlana Kuznetsova 6-4, 6-4.
French 13th seed Richard Gasquet, a semi-finalist three years ago, was the day’s biggest casualty.
Vesely had never beaten a top-10 foe before defeating Djokovic 6-4, 2-6, 6-4.
Seventh seeded Italian Vinci, defeated by compatriot Flavia Pennetta in last year’s final, eased past Christina McHale of the United States 6-1, 6-3.
Kvitova now plays Ukrainian 22nd seed Elina Svitolina who put out Lauren Davis of the United States 6-1, 4-6, 6-3.
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Later Wednesday, Spanish fourth seed Rafael Nadal, the 2010 and 2013 champion, takes a 7-1 career record over Italy’s Andreas Seppi into their night time clash. And third-seeded Garbine Muguruza, who won the French Open, faces Anastasija Sevastova.
