Lucas Pouille outlasted 14-time Grand Slam champion Rafael Nadal in a five-set classic on Sunday to lead a trio of French men into the quarterfinals of the US Open.

Pouille, 22 and ranked 25th in the world, lived up to the promise of his quarterfinal run at Wimbledon, emerging from a roller-coaster ride with a 6-1, 2-6, 6-4, 3-6, 7-6 (8/6) triumph over the Spanish superstar.

The defeat leaves Nadal -- forced out of the French Open third round with a wrist injury that also saw him miss Wimbledon -- without at least one Grand Slam quarterfinal appearance for the first time since he was a teenaged tour newcomer in 2004.

Pouille came out firing, pushing Nadal back with an array of deep groundstrokes and angled shots.

Fifty-two winners from Nadal -- whose attacking response saw him come out a winner on 35 of 48 forays to the net -- weren't enough.

The taut battle came down to the fifth-set tiebreaker and Nadal, trailing 3-6, showed his mettle by saving three match points -- the third on Pouille's serve.

Then he smacked a forehand into the net to give Pouille one more chance and the French player pounced on it with a blazing forehand that kissed the sideline.

The four-hour, seven-minute contest entranced the crowd in Arthur Ashe stadium.

Pouille next tackles 10th-seeded compatriot Gael Monfils, a 6-3, 6-2, 6-3 winner over Cypriot Marcos Baghdatis.

Novak Djokovic steamed into the quarterfinals of the US Open with a 6-2, 6-1, 6-4 victory against 84th-ranked Briton Kyle Edmund.

Edmund, playing in a Grand Slam fourth round for the first time, barely got a look-in during the first two sets against the world number one and defending champion, who booked a last-eight meeting with ninth-seeded Frenchman Jo-Wilfried Tsonga, a 6-3, 6-3, 6-7 (7/9), 6-2 winner over American Jack Sock.

Having raced through the first two sets in just over an hour, Djokovic sought treatment after surrendering his first service break of the night -- starting a run of three straight games for Edmund that gave the Briton a 3-2 lead.

Djokovic put the set back on serve with a break for 3-3, and broke Edmund at love to close out the match.

Caroline Wozniacki, derailed this year by an ankle injury which sent her career into a tailspin, and Anastasija Sevastova, who quit the sport three years ago, set up a US Open quarterfinal duel.

Former world number one Wozniacki, the runner-up in 2009 and 2014, downed American eighth seed Madison Keys 6-3, 6-4 to make the last-eight in New York for a fifth time.

Sevastova became the first Latvian woman in 22 years to reach a Grand Slam quarterfinal when she beat British 13th seed Johanna Konta 6-4, 7-5.

The other quarterfinal in the bottom half of the draw sees German second seed Angelique Kerber face Roberta Vinci, the Italian seventh seed.

Kerber defeated Petra Kvitova 6-3, 7-5 while Vinci enjoyed a 7-6 (7/5), 6-2 win over Lesia Tsurenko of Ukraine.

Monday's action 

Juan Martin del Potro became the lowest ranked man since 1991 to reach the US Open quarter-finals when opponent Dominic Thiem retired from their last-16 tie through injury on Monday.

The 142nd-ranked Argentine was leading 6-3, 3-2 when the eighth-seeded Austrian quit with a knee injury.

Jimmy Connors was ranked 174 when he went on to the US Open semi-finals in 1991.

At the Women's singles, Fifth-seeded Romanian Simona Halep advanced to the quarter-finals  for the second straight year with a 6-2, 7-5 victory over Spain's Carla Suarez Navarro.