(CNN) -- Fifth seed Jo-Wilfried Tsonga crashed out of the U.S. Open in the second round Thursday, beaten 6-4 1-6 6-1 6-3 by Slovakia's Martin Klizan.
France's Tsonga put up a lackluster display to become the first major casualty of the final grand slam of the season.
Tsonga, who reached the quarterfinals at Flushing Meadows last year, was due to face Britain's Andy Murray at the same stage this year, his exit potentially easing the path of the Olympic champion.
Murray will face Feliciano Lopez in the third round after the Spanish veteran beat compatriot Pablo Andujar 6-4 6-1 6-7 3-6 7-5 in a five-set epic.
World No.52 Klizan was reaching that stage of a grand slam for the first time and will face either 32nd seed Jeremy Chardy of France, who beat Murray in Cincinnati, or Australia's Matthew Ebden.
He stunned Tsonga with a display of attacking tennis and quickly took a one set lead.
Tsonga looked to have restored confidence in the second set until Klizan restored his advantage in the third.
The Slovakian opened up a 4-0 lead in the fourth set and although Tsonga broke back to reduce the lead to 4-3, he closed it out in style.
Earlier Thursday, Spain's 11th seed Nicolas Almagro battled past Philipp Petzschner of Germany 6-3 5-7 5-7 6-4 6-4.
Japan's Kei Nishikori, the 17th seed also made the last 32 with a 6-2 6-2 6-4 win over home qualifier Tim Smyczek.
U.S. hopes were boosted by a superb win by 23rd seed Mardy Fish over Russian Nikolay Davydenko.
Fish battled back from two sets down to beat Davydenko 4-6 6-7 6-2 6-1 6-2 in three hours 26 minutes.
12th seed Marin Cilic of Croatia was also taken the full distance by Daniel Brands of Germany before winning 6-3 6-2 5-7 4-6 7-5
Top seed Roger Federer was playing Bjorn Phau of Germany in the night session.