Rafael Nadal picked off another opponent at the U.S. Open – and is that much closer to defending his title.

The Spaniard defeated Andy Roddick in the quarterfinal matchup in straight sets, 6-2, 6-1, 6-3, on Friday to reach the semifinals at Flushing Meadows for the fourth consecutive year.

Nadal compiled a stunning 22-0 edge in forehand winners and broke Roddick six times.

Nadal took the first four games against the 2003 U.S. Open champion thanks to two service breaks in the opening 18 minutes, then took 16 of the last 17 points to close the second set. In the third set, Roddick had both of his legs massaged by a trainer during a medical timeout.

In Saturday's semifinals, Nadal will face No. 4 Andy Murray.

For his part, 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," said Murray, who has won his past 10 matches.

While Murray is a three-time Grand Slam runner-up, Isner was playing in his first quarterfinal at a major tournament, and he acknowledged afterward that jitters affected him at the outset.

"I wasn't swinging out like I felt like I should have early on in the match. I was just guiding the ball," said Isner, who lives in Tampa, Fla. "That was a little bit of nerves. It just took awhile to free up."

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.

"It's been a good run for me, but I'm still disappointed right now," Isner said. "I'm not satisfied."

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 what he later called a "gimme 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 prolong the match by winning that set, capping it with a 139 mph ace, while first lady Michelle Obama looked on from the stands.

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.

"More so than his return is everything after the return," Isner said. "He'll block the serve back and then he'll just — he plays incredible defense. That's what he does."

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.

"He reflexed it. I mean, how often does he make that shot? Probably not more than 50 percent," Isner said. "If I get that point there, I like my chances to serve it out. We'd still be out there right now."

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.

"I didn't play a good game there," Isner said, "and I paid the price for it, that's for sure."

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.

"I played well in the third and fourth set," Isner said. "Just didn't go my way at the end."

Based on reporting by The Associated Press.

Follow us on twitter.com/foxnewslatino
Like us at facebook.com/foxnewslatino