American crowd favorite John Isner toppled world No. 1 Novak Djokovic in Friday's quarterfinal action at the $3 million Western & Southern Open, a hardcourt ATP Masters 1000 event.

The unseeded Isner knocked out the four-time Cincinnati runner-up Djokovic in three sets, 7-6 (7-5), 3-6, 7-5, at the Lindner Family Tennis Center. The tight match was decided when the towering American broke the Serbian star in the final game of the bout.

Isner, who was a hardcourt runner-up in Washington, D.C., two weeks ago, is now 2-3 lifetime against Djokovic, with the other victory coming at a Masters event in Indian Wells, Calif., last year.

Djokovic lost to five-time Cincy champion Roger Federer in last year's marquee finale here.

This is the only Masters tournament that Djokovic has failed to win. He was the runner-up four of the last five years.

Seventh-seeded former U.S. Open champion Juan Martin del Potro held off oft- injured Russian veteran Dmitry Tursunov, 6-4, 3-6, 6-1. Del Potro beat Isner in the recent D.C. finale and will face the 6-foot-9 American once again in Saturday's semifinals.

This is the last Masters tournament before the U.S. Open, which will commence August 26 in New York.

The 2013 Cincinnati champ will collect $583,800.