French fifth seed Jo-Wilfried Tsonga became the first major casualty of the US Open on Thursday when he slumped to a 6-4, 1-6, 6-1, 6-3 defeat to unheralded Slovak Martin Klizan.
Tsonga, who made the quarter-finals in 2011, had come into the final Grand Slam event of the season in a fog of injury and form worries summed up by having to skip the Cincinnati event after cutting his knee on a fire hydrant.
His defeat was good news for British third seed Andy Murray, the Olympic champion, who had been due to face the Frenchman in the semi-finals.
Left-hander Klizan, the world No.52, progressed to the third round of a Grand Slam for the first time and will tackle either 32nd seed Jeremy Chardy of France or Australia’s Matthew Ebden.
Klizan only won his first career Grand Slam match this year at the French Open, spending most of his time on the second-tier Challenger tour where he won four titles this season.
But he shrugged off that inexperience, firing 32 winners to help offset the 42 unforced errors he sent down in a daring display of attacking tennis.
Elsewhere, Spanish 11th seed Nicolas Almagro fought back to beat Philipp Petzschner 6-3, 5-7, 5-7, 6-4, 6-4 with the German’s challenge undone by 62 unforced errors.
Japan’s 17th seed Kei Nishikori also made the third round with a 6-2, 6-2, 6-4 win over American qualifier Tim Smyczek.
Serbia’s Ana Ivanovic reached the third round, but admitted she needs to take painkillers every morning to see her through the season’s last Grand Slam tournament.
The 12th-seeded Serb, who has never got beyond the fourth round in New York, made the last 32 with a 6-2, 6-2 win over Sofia Arvidsson of Sweden.
But the 2008 French Open champion is still bothered by a right foot injury which forced her out of the Cincinnati tournament on the eve of the US Open.
“I still have to take a handful of pills every morning,” said the 24-year-old.
“It was a little bit unfortunate but it’s part of the sport. We play so much and changing surfaces and continents. My foot has been healing and at the moment I am feeling healthy.”
Ivanovic goes on to face either America’s Sloane Stephens or German qualifier Tatjana Malek for a place in the last 16.
Fellow Serb Jelena Jankovic, seeded 30th and the 2008 runner-up, also made the third round with a 6-4, 6-2 win over Spain’s Lara Arruabarrena-Vecino.
She next meets either second seed Agnieszka Radwanska of Poland, the Wimbledon runner-up, or Spain’s Carla Suarez Navarro.
Russian 14th seed Maria Kirilenko, watched by ice hockey superstar boy friend Alex Ovechkin, saw off Hungarian 33-year-old Greta Arn 6-3, 6-2.
Slovakian 13th seed Dominika Cibulkova, a quarter-finalist in 2010, edged Serbia’s Bojana Jovanovski 7-6 (7/3), 7-6 (7/3).