US Open 2017: Marin Cilic & John Isner go out in the third round

Diego Schwartzman had never gone past the second round at the US Open

Former champion Marin Cilic suffered a surprise third-round loss to Argentina's world number 33 Diego Schwartzman at the US Open.

Fifth seed Cilic lost 4-6 7-5 7-5 6-4 as Schwartzman reached the fourth round of a Grand Slam for the first time.

The Croat was playing his first event since losing July's Wimbledon final to Roger Federer, because of injury.

Tenth seed John Isner became the fifth top-10 seed to go out as he lost to Mischa Zverev.

Germany's Zverev, the 23rd seed, played superbly to beat the American 6-4 6-3 7-6 (7-5) in the night session.

Isner's compatriot, Sam Querrey, did make it through with a 4-6 6-2 6-4 6-4 win over Moldova's Radu Albot.

Before the defeats for Isner and Cilic, there had already been early exits for fellow top-10 seeds Alexander Zverev, Grigor Dimitrov and Jo-Wilfried Tsonga.

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Cilic, 28, who claimed the US Open title in 2014, was broken nine times, including four times in the third set, to ensure there are no former title winners in the bottom half of the draw.

It guarantees there will be a first-time US Open finalist.

"I think many players are doing well this week, and they are taking the opportunities because many players are injured this week," said Schwartzman, 25.

"I think we are trying to take the chances and try to go forward in the tournament."

Cilic missed the tournaments leading up to the US Open because of an adductor strain and had not played since the Wimbledon final, when he struggled with a blister on his left foot.

"[The injury] played a quite significant part [in the defeat], and just being injured and not being able to keep that good form," Cilic said. "I was struggling with my shots and my serve was off."

Schwarzman will play 16th seed Lucas Pouille after the Frenchman beat Mikhail Kukushkin of Kazakhstan 2-6 6-3 6-4 6-4.

Spanish 12th seed Pablo Carreno Busta beat Nicolas Mahut of France 6-3 6-4 6-3 to reach the fourth round at Flushing Meadows for the first time.

He will play Canadian 18-year-old Denis Shapovalov, who went through when Britain's Kyle Edmund pulled out injured.

Croatia's Borna Coric, who knocked out fourth seed Alexander Zverev in the second round, lost to 28th-seeded South African Kevin Anderson 6-4 6-3 6-2.

Anderson will play Paolo Lorenzi after the Italian beat compatriot Thomas Fabbiano.