LONDON -- The last American singles player at Wimbledon, ninth-seeded John Isner, lost in the third round Monday despite hitting 52 aces, beaten by 19th-seeded Feliciano Lopez of Spain 6-7 (8), 7-6 (6), 7-6 (3), 7-5.
Lopez earned the only service break of the match in the next-to-last game with a cross-court backhand passing winner that he celebrated by leaping and punching the air. It was the only time Isner was broken during his three matches this year at the All England Club.
Lopez hit 34 aces Monday and saved the only two break points he faced.
It's the first time since 1911 that no American men or women have reached the round of 16 at Wimbledon.
"Didn't know that," Isner said after the loss. "Don't really care either."
A three-time quarterfinalist at Wimbledon, Lopez is back in the fourth round for the first time since 2011. He'll play Australian Open champion Stan Wawrinka next.
Wawrinka kept up his bid for a second Grand Slam singles title when he claimed a 6-3, 6-3, 6-4 win over Denis Istomin.
The fifth-seeded Wawrinka had 12 aces in the match.
The Swiss player broke Istomin four times in five break-point chances and saved all three break points against him in the 1 hour, 27-minute match.
The first man to reach the quarterfinals was 26th-seeded Marin Cilic of Croatia, who followed up his third-round win over 2010 finalist Tomas Berdych by beating Jeremy Chardy 7-6 (8) 6-4, 6-4. Cilic will next play either top-seeded Novak Djokovic or Jo-Wilfried Tsonga.
The two resumed play at 3-3 in the fifth set after their match had been suspended on Saturday.
The 10th-seeded Nishikori broke in the 10th game of the final set Monday to win 3-6, 6-3, 4-6, 7-6 (4), 6-4.
He will play Canadian Milos Raonic next.
The Associated Press contributed to this report.