No. 3 seed Marin Cilic, the 2017 Wimbledon runner-up, was upset in the second round Thursday, leaving a major opening for American John Isner.
Cilic was also the highest seed (and only remaining Grand Slam winner) that Roger Federer could have faced before the final.
Argentina’s Guido Pella, ranked No. 82 in the world, shocked the Croatian Cilic 3-6, 1-6, 6-4, 7-6 (3), 7-5.
Cilic became the fourth top-10 seed in the men’s draw to go out in the first two rounds. Five of the top eight women have also been upset.
Isner, the top-seeded American at No. 9, could benefit greatly from Cilic’s absence. Isner, who edged Belgian qualifier Ruben Belemans in five sets over two days in the second round, is the highest seed left in his quarter of the draw.
Isner gets 98th-ranked Moldovan Radu Albot in the third round. Isner has never made it past the third round in nine Wimbledon appearances. The biggest potential threats to Isner in the fourth round — No. 6 Grigor Dimitrov and three-time Grand Slam singles champion Stan Wawrinka — were already eliminated.
Isner and Cilic would have played in the quarterfinals. Now, the only seed Isner would face in a potential quarterfinal is No. 13 Milos Raonic, the 2016 Wimbledon runner-up.
Former champions Novak Djokovic and Rafael Nadal remained on course for a semifinal meeting in the other half of the draw.
Djokovic overcame a knee problem to beat Horacio Zeballos 6-1, 6-2, 6-3, while top-ranked Nadal defeated Mikhail Kukushkin of Kazakhstan 6-4, 6-3, 6-4.
Djokovic called for a trainer and had his left leg massaged when leading 4-3 in the third set. But he easily held serve in the next game and broke Zeballos again to close out the match.
“I’ve been doing checkups now. It seems like it’s nothing major,” Djokovic said of the injury. “When I say ‘not major,’ if it was major I’d be pulling out from the tournament. What I’m saying is that it’s most likely a twitch, you know, in the muscle or something like this that has affected the knee a little bit.”
Nadal won only 64 percent of points on his first serve and faced 13 break points — including three in the first game of the match — but he saved 11 of them and converted five of his own to wrap up the win in under 2 1/2 hours on Centre Court.
The 11-time French Open champion is looking for his third title at the All England Club and first since 2010.
Women’s No. 1 Simona Halep also advanced, winning the last 10 games to beat Saisai Zheng of China 7-5, 6-0. Saisai led 5-3 in the first set but Halep broke back for 5-5 and cruised the rest of the way against her 126th-ranked opponent.
The Associated Press contributed to this report.
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