The 61st-ranked Coric screamed in triumph when Zverev sailed a forehand over the baseline to end the match. It was among 58 unforced errors committed by Zverev.
"It's upsetting. Today was upsetting,'' Zverev said. "The way I played was upsetting. The tournament so far is upsetting for me.''
The 18-year-old Canadian knocked off Rafael Nadal at the Rogers Cup earlier this month before falling in the semifinals in his home country.
Isner had 30 aces in a 6-3, 6-4, 7-5 second-round victory over Hyeon Chung of South Korea. The 10th-seeded Isner, who is also the top-ranked American man, never lost his serve and fittingly hit his final ace on match point.
Querrey moved on with a 6-4, 6-1, 6-4 victory over Israel's Dudi Sela. The 17th-seeded Querrey hit 19 aces and collected 35 winners, nearly three times as many as his opponent.
The No. 14 seed from Australia was ousted in the first round with a 3-6, 6-1, 4-6, 1-6 loss.
They had traded sets when Kyrgios called for treatment early in the third, and a trainer came out and massaged his right shoulder. Kyrgios continued but his level of play dropped off severely before he left in frustration, smashing his racket to the court after the match and carrying the busted one with him as he exited.
Also in the third set, Kyrgios got into an argument with chair umpire Carlos Ramos after being warned for using bad language.
Kyrgios pleaded that he hadn't said anything improper, but Ramos said a linesperson had reported to him. Said Ramos: "I cannot repeat what he said you said.''
Kyrgios had arrived in New York with momentum after reaching the finals in Cincinnati and beating Nadal along the way.
"I knew that after I lost the first I knew I had to dig deep,'' Kyrgios said. "Played a great second set. Was feeling good. And then I don't know. I just -- something didn't feel right in my arm.''
When Kyrgios was asked Wednesday whether he plans to continue being coached by former player Sebastien Grosjean, the reply was rather startling -- or rather, would have been, coming from any other professional athlete.
"I don't know, honestly. I'm not good enough for him,'' Kyrgios responded. "You know, he's very dedicated. He's an unbelievable coach. You know, he probably deserves a player that is probably more dedicated to the game than I am. He deserves a better athlete than me.''
When a reporter returned to that topic, asking Kyrgios to explain what he meant, he said: "I'm not dedicated to the game at all.
"I mean, you know what I mean: There are players out there that are more dedicated, that want to get better, that strive to get better every day. The 'one-percenters.' I'm not that guy.''
Asked whether he envisions ever being "that guy,'' Kyrgios answered: "I really don't know. Probably not. Honestly not.''
He then referenced his impressive run in Cincinnati and described his routine there.
"I was playing basketball ... every day for two hours. Like, I played an hour of basketball before I played [2013 French Open runner-up] David Ferrer in the semifinal,'' he said. "I was ... getting a milkshake every day. I was less dedicated. And this week I was dedicated -- and my shoulder starts hurting.''
Austrian Dominic Thiem didn't need long to finish off his first-round victory once play resumed.
The No. 6 seed wrapped up a 6-4, 6-1, 6-1 rout of Australian Alex De Minaur, not long after they returned to the Grandstand. Thiem had won the first two sets and the opening game of the third on Tuesday before their match was halted by rain.
"It was really different, the conditions, between yesterday and today, and my goal was to break immediately, and that's what I did,'' Thiem said.
Also advancing were No. 11 seed Roberto Bautista Agut of Spain over Italy's Andreas Seppi in four sets; No. 15 Tomas Berdych, who beat American Ryan Harrison in straight sets; No. 18 Gael Monfils, who swept past fellow Frenchman Jeremy Chardy; and another Frenchman, No. 30 Adrian Mannarino, a straight-sets winner over Lithuanian Ricardas Berankis.
Elsewhere, Kyle Edmund carried the British flag alone into the third round of the singles at the US Open with another impressive victory.
The British No.2 gained his second straight-sets win of the tournament, defeating American Steve Johnson 7-5 6-2 7-6 (7/4) to book a third-round date with exciting young Canadian Denis Shapovalov.
Edmund said: ''It's a big one to get through. I'm very happy. I came out with my level the way it was, did what I needed to do, the tactics, controlling the match.
He was joined in the second round by Cameron Norrie but his fellow 22-year-old found 12th seed Pablo Carreno Busta too good, the Spaniard winning 6-2 6-4 6-3.
Aljaz Bedene, meanwhile, struggled with a knee problem as he lost his rain-delayed first-round encounter against teenage Russian Andrey Rublev 6-1 6-4 6-4.
In the absence of the injured Andy Murray, and with Johanna Konta and Heather Watson losing in round one, this is Edmund's first experience of carrying British expectations by himself at a grand slam.
The Associated Press and PA Sport contributed to this report.