Next-generation rising stars Alexander Zverev and Nick Kyrgios crashed out of the US Open, even as established players like Marin Cilic and Dominic Theim progressed.

Fourth seed Zverev, whose five ATP titles this year include a win over Roger Federer in this month’s Montreal final, fell to 61st-ranked Croatian Borna Coric 3-6, 7-5, 7-6 (7/1), 7-6 (7/4).

The 20-year-old German had been the highest-ranked player in his half of an injury-hit Open draw.

“It’s upsetting because the draw is pretty open in the bottom part,” Zverev said. “I felt like I should have been the favourite there. I just played a very, very bad match, so it’s unfortunate.”

Coric, who faces South African Kevin Anderson for a last-16 berth, was one point from a fifth set before winning five in a row to force the deciding tie-breaker.

“I was just thinking to keep the points shorter,” Coric said. “And yeah, I was a little bit lucky.”

Zverev’s ouster left US 10th seed John Isner the top-ranked player in his draw quarter and Croatian fifth seed Marin Cilic the best in his half of the draw.

Wimbledon runner-up Cilic, the 2014 US Open winner, reached the third round by beating Germany’s Florian Mayer 6- 3, 6-3, 6-3.

Kyrgios, the 14th seed and former top-rated obstacle in Federer’s quarter-final path, hurt his right shoulder in a 6- 3, 1-6, 6-4, 6-1 first-round loss to 235th-ranked fellow Aussie John Millman.

“Early in the third set I hit one serve and I never felt the same after that,” Kyrgios said. “Something didn’t feel right in my arm.”

Kyrgios, 22, dropped eight of the last nine games.

“Nick’s shoulder deteriorated as the match went on,” Millman said after his first US Open triumph. “It’s a victory but slightly hollow.”

Austrian sixth seed Dominic Thiem ousted Aussie Alex de Minaur 6-4, 6-1, 6-1. Thiem is the highest-ranked rival on the Federer and Nadal side of the draw.

Canadian 18-year-old qualifier Denis Shapovalov defeated French eighth seed Jo-Wilfried Tsonga 6-4, 6-4, 7-6 (7/3) to book a third-round date with Britain’s Kyle Edmund.

“It’s a dream come true for me,” Shapovalov said.

Shapovalov became the youngest man in the third round of a Grand Slam since Bernard Tomic at the 2011 Australian Open and at the US Open since American Donald Young in 2007.

Wimbledon champion Garbine Muguruza reached the US Open third round for the first time by beating China’s 92nd-ranked Duan Ying-Ying 6-4, 6-0.

“I had like a curse and I broke it finally. I’m so happy,” Muguruza said. “I just put the heart on the court. I knew I had to be all the time fighting for the ball and in the end I won.”

Beating Slovakian 31st seed Magdalena Rybarikova to reach the last 16 would make the Spanish third seed the leader in a seven-woman fight for world number one.

Russian eighth seed Svetlana Kuznetsova, the 2004 US Open champion, rescued three match points in defeating 67th-ranked Czech Marketa Vondrousova 4-6, 6-4, 7-6 (7/2) to reach the second round to stay in that hunt.

Ukraine’s fourth-seeded Elina Svitolina did as well, downing 42nd-ranked Czech Katerina Siniakova 6-0, 6-7 (5/7), 6-3.

Another top spot hopeful is seven-time Grand Slam champion Venus Williams, the 37-year-old US ninth seed who beat France’s Oceane Dodin 7-5, 6-4.