MASON, Ohio -- Novak Djokovic dumped another pressure-packed shot into the net and stood in place for a moment, stunned by another upset in Cincinnati.
It's the only place where he can't win.
Top-ranked American John Isner ended Djokovic's attempt to make ATP history Friday, beating the No. 1 player 7-6 (5), 3-6, 7-5 in the quarterfinals at the Western & Southern Open.
Djokovic has never won in Cincinnati, the only Masters event that has eluded him during his career. He has lost in the finals four times, including last year to Roger Federer. All he needs to do is hoist the winner's trophy one time in Cincinnati to become the first player to win all nine Masters events.
Wait until next year. Again.
"It's disappointing that I played this way," Djokovic said. "For me, it's very disappointing."
Isner reached the semifinals in Cincinnati for the first time, knocking off a No. 1 for only the second time in his career. His other No. 1 upset? He beat Djokovic at Indians Wells in the semifinals last year.
"A fantastic win for me," Isner said. "Certainly one of my greatest memories as a tennis player."
He'll play seventh-seeded Juan Martin del Potro, who advanced Friday by beating qualifier Dmitry Tursunov 6-4, 3-6, 6-1. Del Potro is in the semifinals for the second straight year.
Soon after Djokovic got knocked out, No. 2 Andy Murray was gone, too. He failed to convert a break point while losing 6-3, 6-4 to Tomas Berdych, who also beat him in the quarterfinals at Madrid.
They were relegated to the adjoining grandstand court. Both players struggled with the loud music, announcements and cheering from center court.
"I think this was my best moment of the game to handle this because I was struggling with the noise around the court and the distraction," Berdych said. "You know, I handled it pretty well today."
Murray? Not so much. At least it got the Wimbledon champion prepared for Flushing Meadows.
"I think in some ways it's good preparation for the U.S. Open because normally the U.S. Open is fairly loud," Murray said. "You know, a lot of movement and music, and they have the big screen and stuff. So, yeah, you get used to that playing here."
In the women's draw, top-seeded Serena Williams needed only 64 minutes to beat Simona Halep 6-0, 6-4. She'll play Li Na, who advanced to the semifinals automatically when No. 4 Agnieszka Radwanska withdrew to attend her grandfather's funeral.
Like Djokovic, Williams has never won in Cincinnati, which has become one of her goals. She struggles with the conditions on court and wasn't happy with her overall level of play on Friday.
"I have quite a few things on my tennis bucket list," Williams said. "This obviously is one of them. But I like to believe if it doesn't happen this year, I always have another chance."
Also, 14th-seeded Jelena Jankovic beat 12th-seeded Roberta Vinci 6-0, 6-4 to reach the semifinals for the third time. She won the tournament in 2009 and lost the title match to Maria Sharapova in 2011.
"I love playing here in Cincinnati because I have great results in the past," said Jankovic, who fought off eight of nine break points in the second set. "So that always helps. I mean, I was a finalist and a champion before, so you always love coming back to places where you can win."
He played poorly last year in his loss to Federer in the final. He was off again Friday, which was especially frustrating since he came into the tournament motivated to make ATP history.
"I just played a very bad match overall," he said. "Terrible match. From beginning to end, except the start of the second set, I was just a different player totally."
Djokovic wasted a chance to break Isner early in the third set. He was up 40-15 in the final game, ready to send it to a tiebreaker, when he came apart. Isner kept the game going with a running forehand that hugged the line, drawing a loud cheer from the crowd.
"Probably the best shot I hit all match," Isner said.
Djokovic gave Isner his first attempt at a match point by dumping a backhand into the net, but saved it with a 119 mph ace. With the crowd cheering Isner on, Djokovic double-faulted and dumped another backhand into the net, giving Isner his only service break of the match.
"I don't know," Djokovic said.
Del Potro has been playing with a sore wrist and knee, two concerns with the U.S. Open at hand. He managed to reach the semifinals without issue.
"It's bothering me a little bit, but not too much," he said. "(I'm) trying to play a slice and play different shots in this tournament before the U.S. Open to see how different I can play against the top guys or doing different things."
"I'm OK," he added. "My knee is OK, too, and that's important looking forward to New York."