NEW YORK (AP) – Andy Murray ended marathon man John Isner’s best run at a Grand Slam tournament.

The No. 4-seeded Murray dealt with No. 28 Isner’s big serve and used a variety of lobs and pinpoint passing shots to win 7-5, 6-4, 3-6, 7-6 (2) at the U.S. Open on Friday, reaching his fourth major semifinal this season.

Murray, one of tennis’ top returners, weathered 17 aces at up to 140 mph from the 6-foot-9 Isner but repeatedly got back serves topping 130 mph and managed to break the American twice in a row bridging the first two sets.

“It’s so frustrating playing against him because you feel like you’re playing good tennis, and it’s so hard to break him,” Murray said.

While Murray is a three-time Grand Slam runner-up, Isner was playing in his first quarterfinal at a major tournament. To date, Isner is best known for winning the longest match in tennis history, 70-68 in the fifth set in Wimbledon’s first round in 2010, when he pounded 113 aces over its record 11 hours, 5 minutes.

Isner repeatedly has said he aims to be known for a more important victory in the late stages of a top tournament, but that’ll have to wait.

In Saturday’s semifinals, Murray will face defending champion Rafael Nadal or 2003 champion Andy Roddick, who were to play later Friday.

The other semifinal was set up by Thursday’s quarterfinals, and it’ll be a big one: No. 1 Novak Djokovic against No. 3 Roger Federer, who’s won five of his record 16 Grand Slam championships at the U.S. Open.

Djokovic is 62-2 with nine titles in 2011, including at Wimbledon and the Australian Open. His first loss this season came when Federer ended Djokovic’s 43-match winning streak in a thrilling French Open semifinal.

Murray’s past Grand Slam final appearances include losses to Djokovic at the Australian Open in January and to Federer at the U.S. Open in 2008. He’s seeking to become the first British man since 1936 to win a Grand Slam title.

As it is, Murray is now only the seventh man in the Open era to reach at least the semifinals at all four Grand Slam tournaments in a single season. Three of the others are Federer, Nadal and Djokovic.

Trying to push Murray to a fifth set, Isner got the fourth into a tiebreaker, where his serving is usually a significant advantage.

Not this time.

Isner’s play was littered with mistakes down the stretch: He double-faulted to trail 2-1, slapped a gimme forehand volley into the net to make it 5-2, put a drop shot into the net for 6-2, then missed a forehand return on match point, ending things after 3 hours, 24 minutes.

“He put a ton of pressure on me,” Murray said. “It was a relief to win that fourth-set ‘breaker.”

While he doesn’t serve nearly as fast as Isner does regularly, Murray did a good job with that part of his game Friday, hitting 14 aces of his own. After facing — and saving — a break point in the second game of the match, Murray won 42 of the next 51 points he served, helping him grab a two-set lead.

It took nearly two hours of action, but Isner finally did break, going up 2-0 in the third set when Murray sailed a backhand long to lose serve for the only time. That helped Isner extend the match by winning that set, capping it with a 139 mph ace, while first lady Michelle Obama looked on from the stands.

During that set, Isner tweaked his right ankle and appeared to be limping slightly. But when he was visited by a trainer, they only spoke, and Isner didn’t receive treatment.

Rain earlier in the week forced the U.S. Tennis Association to delay the men’s final from Sunday to Monday for the fourth consecutive year, and three of the four men’s quarterfinalists in action Friday were on court for a third straight day.

Friday’s temperature topped 80 degrees, and at the start of play, the blue sky over a mostly empty Arthur Ashe Stadium wasn’t marred by a single cloud. Those conditions favored Murray, whose training regimen includes spending weeks practicing in the heat and humidity of Florida each summer.

He’s also got a more varied game than Isner, who primarily relies on his serve and forehand setting up chances to rush the net, where his significant wingspan can cover a lot of territory. Murray showed off his full repertoire, including lob after lob that would arc over the lanky Isner — no easy task — and curl in near the baseline.

While Isner did win the point on 50 of his 75 forays to the net, Murray found holes through which he was able to zip passing shots off both wings, often on the run.

A key moment came with Isner holding two break points while Murray served at 4-all, 15-40 in the fourth set. By now the stands were more full, and Isner was feeding off the partisan spectators’ energy.

On the first break point, Murray delivered a 129 mph ace. On the next, he hit a second serve that Isner thought might have been a fault — a replay shown on TV showed it caught the back of the service line — and Murray won the point with a stretching half-volley.

Murray eventually held serve there, but he clutched at the small of his back later in that game. In the next game, Murray’s feet got tangled, sending him tumbling to the court, but he quickly rose after losing the point.

At 5-all in the first set, Murray got an opening on Isner’s serve and barged right through. One of Isner’s five double-faults set up break point, and when he pushed a forehand long, Murray had a lead. That was part of nine consecutive points that Murray won on Isner’s serve. That stretch included a break to start the second set, when Murray didn’t make an unforced error until the eighth game.

But Murray’s level began to sag a bit in the third set, while Isner elevated his play, making things far more interesting — until the lopsided tiebreaker.

Copyright 2011 The Associated Press.

Watch & Listen LIVE