Number three Nadal booked a spot in the semi-finals by rallying past Federer, with the Swiss player saving four match points in a 5-7, 6-4, 6-3 loss. The pair have met a total of 31 times, with Nadal winning 21 of those.
"My movement got better, with more intensity," said Nadal, undefeated on hardcourts in 2013. "I put in more balls on the return, and controlled the baseline, something that didn't happen the first set and a half. The match was very close. I played some good points in important moments."
Federer suffered only his second loss in the last five editions in Cincinnati. "Credit to him for hanging in and getting back some tough shots," said five-time champion Federer, who will fall to seventh in the world as a result of his defeat. "I have some disappointment, I could have played better late in the second and early in the third. "But my tactics were working most of the time. I served well for most of the match, but when I didn't he was able to step it up."
World number one Djokovic fell 7-6 (7/5), 3-6, 7-5 to unseeded John Isner as the Serb's attempt to set another tennis record ended in defeat. Had Djokovic beaten the American he would have kept alive a bid to become the first man to win all nine Masters 1000 titles in his career. Two-time champion Murray was eliminated 6-3, 6-4 by Tomas Berdych, leaving the Scot to head for New York and his US Open title defense, beginning August 26, with plenty to work on.
The second seed fired 10 aces but was betrayed as he missed on all four of his break points. Berdych has now beaten Murray twice this season after beating him in Madrid on clay. "The court was lively today. It was bouncing pretty high and it was quite tough to control the ball. I made too many errors," said Murray.
"The first couple of rounds, I was able to hit the ball quite flat and wasn't kind of flying on me; today it was happening a little bit. "I need to make sure I'm not making too many mistakes going into the US Open." Isner set up a Saturday semi with 2009 US Open winner Juan Martin del Potro, who beat qualifier Dmitry Tursunov 6-4, 3-6, 6-1.
Del Potro said he won despite dealing with pain in his left wrist. The Argentine missed much of the 2010 season with a wrist problems and remains cautious. "Yes, it bothers me a little bit, but not too much," said the 2009 US Open champion. "I'm trying to play slices and different shots before the US Open to see how different I can play against the top guys." Del Potro needed one and three-quarter hours to get past veteran Russian Tursunov, with the Argentine hammering 15 aces and breaking three times. Del Potro reached the semi-finals in 2012 where he lost to Djokovic.
The women's quarter-final matches were dominated by world number one Serena Williams, who raced through a 16-minute opening set en route to an easy 6-0, 6-4 win against Romanian Simona Halep. Williams next plays holder Li Na, after the Chinese fifth seed advanced a day earlier when Agnieszka Radwanska withdrew to attend the funeral of her grandfather in Poland.
Former world number one Jelena Jankovic beat Italy's Roberta Vinci 6-0, 6-4 to reach a fifth semi-final this season. She will next play second seed Victoria Azarenka, who eliminated Caroline Wozniacki 6-3, 7-6 (7/5) in a night match. The win was only the third in nine meetings for Azarenka against Wozniacki.