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 man or woman has 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 will play Australian Open champion Stan Wawrinka next.
Murray's match finished with the Centre Court roof shut after a brief rain delay early in the second set.
The third-seeded Murray has won all 12 sets he has played in the tournament this year, dropping only 32 games. His All England Club winning streak is 17 matches, including the run to a gold medal at the 2012 London Olympics.
Next up for Murray will be No. 11 Grigor Dimitrov, who swept past Argentina's Leonardo Mayer 6-4, 7-6 (6), 6-2 on Court 1 to reach the Wimbledon quarterfinals for the first time. He's also the first Bulgarian man to get this far at the All England Club.
"All of the matches are tough," Murray said. "Everyone that's in the quarterfinals of Slams, they're playing top tennis. I just have to do what I've got to do and concentrate on my side of the court. If I play well, I'll make it tough for them."
In 2013, Murray became the first British man in 77 years to win Wimbledon.
Anderson was trying to reach his first Grand Slam quarterfinal. He would have been the first man from South Africa to get to Wimbledon's quarterfinals since Wayne Ferreira in 1994.
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 Djokovic.
Djokovic, the 2011 champion who lost in last year's final to Murray, hit a cross-court backhand service return on the first match point and held out his arms in a look-at-me pose. It was originally called out, but Djokovic challenged and the replay showed the ball landed on the line.
He broke the 14th-seeded Tsonga twice and saved both break points he faced.
The two resumed play at 3-3 in the fifth set after their match had been suspended 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.