The match was close throughout, but it was the American who prevailed 7-6(5), 3-6, 7-5.
It is Isner’s second win against Djokovic. His first came when he defeated the Serb at Indian Wells last year 6-7(7), 3-6, 7-6(5), a scoreline reminiscent of this latest victory.
“It’s very similar,” said Isner. “I guess the only real difference is this was the quarter-finals, that was the semi-finals. Both matches extremely close, and I really feel like the crowd in both matches really, really helped me out. It was just so much fun to play out there. It's one of the reasons why I work so hard to be able to be in a situation like that and to sort of enjoy it.”
In the first set, Djokovic double faulted to go down a mini-break in the tie-break, and Isner held on to the lead to take the set. The top-ranked American also had seven break points in the second set, including the first game, but it was Djokovic who converted one of his three chances to even the match.
In the third set, Djokovic saved a match point at 5-6 with an ace, but double faulted on the next point and could not save a second.
"Today I wasn't able to capitalise on my opportunities and serves. You know, in some important moments some double faults, and that's the way it is," said Djokovic. ''These conditions here, very fast, and it's very difficult to return. I mean, you can see he didn't give me second serves in the third set.''
Isner got in 74 percent of his first serves during the match, improving from 61 percent in the first set to 84 percent in the third, and won more than 80 percent of those points. But the American also put his opponent under pressure when returning, earning 10 break points and breaking in the last game.
"I think I was able to put a little bit of pressure on him. It didn't really pay off until the very end, but little things like me running around on second serves and hitting big forehands," said Isner.
Isner will meet Juan Martin del Potro in the semi-finals. The pair faced off two weeks ago in Washington, with del Potro winning in three sets.
"I hope I can just do a few things differently. I feel like I'm a bit fresher now than I was then, as I was coming off back to back events at that time. But he was certainly the better player," said Isner, who is currently the leader in the Emirates Airline US Open Series standings. "Just as today, I'm going to have to play very well if I want to win."