Dane Sweeny stuns Lorenzo Musetti in US Open second-round upset

Dane Sweeny has won a real-life David-versus-Goliath battle to rock the US Open with a stunning second-round upset over dual grand slam semi-finalist Lorenzo Musetti.

The unheralded Australian wildcard took down the 14th seed 3-6, 6-1, 6-2, 6-2 on Friday morning (AEST) for the biggest win of his career.

Standing only 170cm high, Sweeny rose to the occasion to reach the third round of a grand slam for the first time and earn a minimum pay day of $US290,000 ($A402,750).

For a couple of heady hours it looked like his underdog countrymen Tristan Schoolkate and Alexei Popyrin would join Sweeny in round three.

But Schoolkate's inspired run from qualifying finally came to a halt at the hands of fifth-seeded French Open runner-up Flavio Cobilli.

Schoolkate snatched the first set before the Italian showed his class to prevail 3-6, 6-3, 6-4, 7-5 after two hours and 41 minutes in New York's scorching summer heat.

And two years after upstaging Novak Djokovic in the US Open's third round, Popyrin fell short of a place in the last 32 once again, losing a tense four-set battle with Chilean Alejandro Tabilo.

Like Schoolkate, Popyrin took the opening set before the 25th-seeded South American claimed two pivotal tiebreakers, then the match 2-6, 7-6 (7-4), 7-6 (7-3), 6-2 to seal a likely third-round date with German top seed Alexander Zverev.

But ranked more than 100 places below his world number 14 opponent, Sweeny is savouring a mighty breakthrough after bossing Musetti into submission.

He ran the 14th seed ragged and had the Italian looking in particular distress when he required a medical time-out after falling behind a double break at 0-3 in the all-important third set.

Even after clawing one break back, Musetti — who has made the Wimbledon and French Open semi-finals over the past two years — continued remonstrating animatedly to his courtside box.

Despite sporting a massive ice pack on his right elbow after his first-round win, Sweeny continued diving like Boris Becker for acrobatic winning volleys at the net.

And the 25-year-old was duly rewarded with a last-32 shot at another Italian, world number 22 Luciano Daredri on Saturday (AEST) — and a rankings rise to a career-best 115 in the world, or better.

"I'm just grateful to be even able to compete in grand slams. The tennis journey is such a rollercoaster," Sweeny said.

"And to soak up the atmosphere and get a win, a couple of wins, in front of this crowd, is awesome."

Australia's sixth seed Alex de Minaur was scheduled to play Dutchman Botic van de Zandschulp on The Grandstand after Schoolkate's match.