NEW YORK — Rafael Nadal kept making a stand, kept coming back, kept showing he would not depart quietly from this U.S. Open. Facing a much younger, much less accomplished opponent, Nadal twice erased a set deficit. Then he staved off a trio of match points.

And then, more than four hours into the toughest test he has put his left wrist through since returning from injury, Nadal faltered. He missed a short forehand, pushing it into the net. Nadal covered his eyes with both hands. One point later, it was over.

The No. 4-seeded Nadal was upset in the U.S. Open's fourth round by 24th-seeded Lucas Pouille of France 6-1, 2-6, 6-4, 3-6, 7-6 (6) on Sunday, prolonging the 14-time Grand Slam title winner's quarterfinal drought at major tournaments.

This was Pouille's third career victory in a five-setter — and all have come in his past three matches.

Since losing in last year's French Open quarterfinals, Nadal has failed to make it beyond the fourth round at a major.

Pouille was joined in the quarterfinals by a pair of countrymen, No. 9 Jo-Wilfried Tsonga and No. 10 Gael Monfils, giving France three members of the men's quarterfinals at the American Grand Slam tournament for the first time in 89 years.

The other quarterfinal on that side of the draw will feature Tsonga against No. 1 Novak Djokovic or 84th-ranked Kyle Edmund of Britain.

Tsonga got there by eliminating the last American man in the field, No. 26 Jack Sock, 6-3, 6-3, 6-7 (7), 6-2.

In the women's draw, Anastasija Sevastova upset 13th-seeded Johanna Konta 6-4, 7-5 to become the first Latvian woman to make the final eight at a Grand Slam since Larisa Savchenko in 1994.

Sevastova will face two-time U.S. Open runner-up Caroline Wozniacki, a 6-3, 6-4 winner over eighth-seeded Madison Keys.

Roberta Vinci, seeded seventh, topped 99th-ranked Lesia Tsurenko 7-6 (5), 6-2 to reach the quarterfinals for the fourth time in five years.