New York: Rafael Nadal was knocked out in the third round after losing a five-set thriller to Italian Fabio Fognini, while top seed Novak Djokovic and defending champion Marin Cilic advanced to the pre-quarterfinals at the US Open here.

Nadal, 29, the winner of 14 Grand Slam titles, won the first two sets, but lost the next three as he was beaten 6-3, 6-4, 4-6, 3-6, 4-6 in a three-hour-46-minute tie on Friday evening.

The 28-year-old World No.32 Fognini will now face Spain’s Feliciano Lopez.

Djokovic meanwhile, beat 25th seed Andreas Seppi of Italy 6-3, 7-5, 7-5 while Cilic battled past Kazakhstan’s Mikhail Kukushkin 6-7 (5-7), 7-6 (7-1), 6-3, 6-7 (3-7), 6-1.

The eighth-seeded Nadal looked to be cruising, leading two sets to love, before the Italian surged back to claim his third victory over the Spaniard this year.

After dropping the first two sets, Fognini turned in one of the most breathtaking shot-making displays of the year. He clubbed forehand and backhand winners from all parts of the court with exquisite timing that belied the amount of effort behind them.

He also attacked the net regularly, winning 39 of 52 approaches.

In a rollercoaster final set, the players held their opening serves but then exchanged seven consecutive breaks before Fognini served out the match from 5-4.

Earlier, in a pulsating eighth game of the final set, Nadal rallied from 40-0 on Fognini’s serve and ultimately saved four game points before leveling the set at 4-4. But Fognini responded with four clean winners to break the Spaniard to love.

“I can’t describe how happy I am. It was very tough. To do it against Rafa, two sets down. It was an incredible match,” Fognini was quoted as saying by atpworldtour.com.

Nadal was all praise for his opponent after the match.

“He played great. It was not a match that I lost, even if I had opportunities. It’s a match that he won. So accept. I’m not happy that he played better than me, but that’s what happened,” the Spaniard said.

Djokovic meanwhile, was broken for the first time at the US Open, but recovered to post his 203rd Grand Slam win.

He is sixth on the all-time list tied with Pete Sampras, and second among current players behind Roger Federer.

Seppi surprised Djokovic with an early break in the first set, but the 2011 champion responded immediately and secured a one-set lead after 41 minutes.

In the second set, both players held their serve before Djokovic raised his level on the return at 5-5, extending the game to 13 points before securing the break.

The World No. 1 struggled to reach the finish line, needing to serve for the match twice.

Cilic also ran into a tough opponent in Kukushkin and the Croatian was made to toil hard before earning his spot in the pre-quarterfinals.

Kukushkin struck 62 winners to Cilic’s 55 over the course of the four-hour, 11-minute duel, but the defending champion’s superior serves enabled him to advance.

Cilic also smashed 27 aces to Kukushkin’s 11; the Kazakh also put just eight of 24 first serves in play in the fifth set, leading to two crucial late-match service breaks for the Croatian.

In other third-round action in men’s singles, 19th seeded Frenchman Jo-Wilfried Tsonga cruised past Ukrainian Sergiy Stakhovsky 6-3, 7-5, 6-2 and talented Frenchman Benoit Paire routed 26th seeded Spaniard Tommy Robredo 7-6 (7-3), 6-1, 6-1.

In women’s third round singles matches, American two-time champion Venus Williams, the 23rd seed, rolled past 12th seeded Swiss Belinda Bencic 6-3, 6-4 and Estonian Anett Kontaveit topped American Madison Brengle 6-2, 3-6, 6-0.

France’s Kristina Mladenovic topped Russian Daria Kasatkina 6-2, 6-3, 13th seeded Russian Ekaterina Makarova defeated Ukrainian Elina Svitolina 6-3, 7-5 and Italian Roberta Vinci stopped Colombian Mariana Duque Marino 6-1, 5-7, 6-2.