Novak Djokovic spent return games squinting at the sun, trying to read John Isner’s 130 M.P.H. serves blurring toward him. One point from forcing a third-set tiebreaker, Djokovic finally blinked.

A resourceful Isner showed some timely defense and exploited a Djokovic double fault and backhand error to earn his lone break in the last game, completing a 7-6 (5), 3-6, 7-5 victory that sends him to the Cincinnati semifinals.

Cincinnati is the only Masters event Djokovic has not yet won, and he looked unsettled from the early stages. Playing his sixth straight quarterfinal, Djokovic had won three of four prior meetings with Isner, but the 22nd-ranked American burst out of the blocks quickly, dropping just two points in his first three service games and earning a pair of break points in Djokovic’s opening service game. Surprisingly, Isner stood his ground and even got the best of the top seed in some of the longer baseline exchanges. A jittery Djokovic began to settle down, holding at love in three of his final five service games to send the opener into the inevitable tiebreaker.

The 6’10” Isner looms so large it must look like he’s serving from atop a step ladder at times. His ability to hold emphatically and his tiebreak prowess—he entered the match with an ATP-best 30-11 record in breakers this season—shrinks his opponents' margin of error while intensifying pressure for even elite adversaries. At 3-all in the breaker, Djokovic spun a double fault into net to hand Isner the mini-break. A massive second serve followed by a smash brought Isner to triple set point, and he closed out the set with a devious kick serve Djokovic could not control.

Djokovic denied four break points in the first game of the second set. Isner set up for a mid-court overhead, but was a bit too careful, striking a controlled smash that Djokovic repelled. When the Serbian dug out a hard-fought hold, Isner was hunched over near the baseline, hands on hips, sucking air like a weary marathoner facing more mileage to reach the finish line.

Drained from that game, Isner dropped serve at 15 to fall into a 2-0 hole. Djokovic fended off break point in the seventh game, eventually sliding an ace down the middle to hold for 5-2.

The two-handed backhand is Djokovic’s signature shot, but he wasn’t nearly as sharp off that side today, scattering some backhands beyond the baseline and lining some into the net, and he punctuated one miss barking at himself and slapping his thigh with his hand. Such uncharacteristic inconsistency would plague Djokovic later on.

Both men saved break points in the decider—Djokovic fought off a break point for 1-all, and Isner blasted a 135 M.P.H. missile to fend off a break point and hold for 4-3—and another tiebreaker seemed certain when Djokovic built a 40-15 lead when serving at 5-6. But a stretched-out Isner slid a running forehand pass up the line for 40-30, then earned his first match point on successive Djokovic backhand errors.

Djokovic saved it with an ace, but spun a double fault deep to give Isner a second match point. A tense Djokovic then netted a timid backhand, as Isner sealed his second win over the No. 1 following his 7-6 (7), 3-6, 7-6 (5) triumph in last year's Indian Wells semifinals. Isner will face Juan Martin del Potro for a spot in the final, a rematch of this year's Washington, DC final, which the Argentine won in three sets.