MASON, Ohio -- Top-seeded Novak Djokovic was upset by Tommy Robredo 7-6 (6), 7-5, in the round of 16 at the Western & Southern Open on Thursday.
The 16th-seeded Spaniard beat a top-ranked player for the second time in his career. The first time, he edged Lleyton Hewitt in the 2003 French Open.
"When I finish my career, and when I will be sitting at home and talking with friends, I will remember days like this," Robredo said.
Djokovic, who has never won the tournament, dropped the first set after fighting back from a 6-3 deficit in the tiebreaker. Robredo took the set with an ace that Djokovic challenged. The replay showed the ball caught the slimmest sliver of the line.
Robredo failed to convert two match points before completing the victory with a slam on Djokovic's short lob.
"It's disappointing that I'm finishing Cincinnati again with a tough loss, but it's the sport," said Djokovic, who lost in the third round at Toronto last week. "I didn't play well in Toronto, didn't play well here. Hopefully, it's going to be different in New York (at the U.S. Open)."
Robredo had lost six straight matches against the Serb after winning their first encounter.
"I knew that if I wanted to win I had to go for it, and try to hope that he will not play his best match," Robredo said. "Both things happen and then I could win."
Earlier, Andy Murray fought off two late match points and edged John Isner of the U.S. 7-6 (3), 6-4, 7-6 (2) to reach the quarterfinals.
Isner, who lost to Rafael Nadal in last year's final, had two chances to win the match with a 6-5 lead in the third set, but Murray salvaged both points before taking control with a mini-break for a 3-1 lead in the tiebreaker.
Stan Wawrinka shook off losing the first set to roll through the next two and advance with a 3-6, 6-0, 6-1 win over Marin Cilic of Croatia. Wawrinka, the Australian Open champion, will meet unseeded Julien Benneteau of France in the quarterfinals.
Benneteau eliminated Jerzy Janowicz of Poland 7-5, 6-1. Fabio Fognini of Italy also needed three sets to get past Yen-Hsun Lu of Taiwan 3-6, 6-3, 6-3, and Milos Ranoic of Canada held off wild card Steve Johnson of the U.S. 6-7 (6), 6-3, 7-6 (4).
In women's play, top-seeded Serena Williams continued her pursuit of her first title in this tournament with a 6-2, 6-2 win over Flavia Pennetta. Williams immediately took command, breaking Pennetta's first serve of the match. Williams, who's never won this tournament, also led, 5-0, in the second set.
"I got the early break, and I didn't let go," she said. "That's what I wanted to do. She can try and come back. She tried to come back, I wanted to stay focused."
Simona Halep of Romania also reached the quarterfinals with a 6-4, 7-5 win over Lucie Safarova of the Czech Republic, but Carla Suarez Navarro of Spain was upset by unseeded Elina Svitolina of Ukraine 4-6, 6-4, 6-4. Halep and Maria Sharapova will meet in the quarterfinals - a rematch of the French Open final won by Sharapova. The fifth seed advanced with a 6-4, 7-6 (2) win over Anastasia Pavlyuchenkova of Russia. Jelena Jankovic also moved on with a 7-6 (4), 6-4 win over Sloane Stephens of the U.S.