Fourth-seeded Andy Murray, left, is congratulated by 6-foot-9 John Isner after his 7-5, 6-4, 3-6, 7-6 (7-2) victory in the quarterfinals of the U.S. Open. Murray, still seeking his first Grand Slam singles title, faces second-seeded Rafael Nadal next. (Stan Honda/AFP via Getty Images)

After a shaky start, John Isner played some of the best tennis of his career Friday at the U.S. Open. Andy Roddick, hampered by a strained thigh muscle and head-to-toe fatigue, could barely mount a credible fight.

By nightfall, the two remaining Americans were out of the U.S. Open, ceding center stage to the world’s top four players — Novak Djokovic, Rafael Nadal, Roger Federer and Andy Murray — who have used Arthur Ashe Stadium these last two weeks to demonstrate anew how vast the gulf is between their abilities and everyone else’s.

It’s the first time since 1992 that all four top seeds have reached the U.S. Open’s men’s semifinals. That year’s quartet consisted of Jim Courier, eventual champion Stefan Edberg, Pete Sampras and Michael Chang.

Friday, on a sun-drenched afternoon, the fourth-seeded Murray overcame a spasm of sulkiness and Isner’s potent serve to secure his place in the semifinals with a 7-5, 6-4, 3-6, 7-6 (7-2) victory.

Nadal, the tournament’s defending champion and No. 2 seed, joined him soon afterward, overpowering Roddick, the 2003 U.S. Open champion, in every conceivable statistical category for a 6-2, 6-1, 6-3 rout.

“You feel helpless,” said Roddick, 29, who entered the tournament with limited preparation, having been sidelined in July by a torn abdominal muscle and having depleted his energy reserves in a four-set slugfest Thursday. “I think you’d rather be booed than hear silence. You know, it’s an empty feeling.”

Having secured their berths among the final four on Thursday, the top-seeded Djokovic and Federer, a five-time U.S. Open champion, reveled in a day’s rest.

They’ll square off in Saturday’s first semifinal, scheduled for noon at Arthur Ashe Stadium. Nadal will take on Murray afterward, with the men’s final pushed back to Monday for the fourth consecutive year because of rain delays earlier in the tournament.

The Murray-Isner clash was the more compelling offering on Ashe on Friday, pitting one the game’s better returns of serve (Murray’s) against the tournament’s biggest serve (Isner’s). The American entered his first Grand Slam quarterfinal with a tournament-high 77 aces in his four previous matches.

The 6-foot-9 Isner has a body engineered for one stroke (the serve), and he has adapted it to others through hard work, developing a dangerous forehand, as well.

The 6-3 Murray, by contrast, has an array of options — drop shots, lobs, down-the-line backhand passing shots, authoritative volleys, spins, slices and intuitive return of serve. But the Scot needed patience, above all, to weather Isner’s big serve.

Murray finally broke in the eighth game of first set and again to open the second set, setting up a two-sets-to-none lead.

Isner broke Murray on a rare error by the Scot (just his 13th gaffe in nearly two hours of play) and went on to win the third set.

Murray turned grumpy soon after, addled by suspect line calls and late-arriving fans. But he reined in his wandering focus to close out the match with a solid performance in the fourth-set tiebreak, with Isner double-faulting, flubbing an easy volley and plowing a shoe-top volley into the net.

Like Nadal, Murray will play his third best-of-five-sets match in three days on Saturday. But Murray took longer and expended more energy to get there, needing 3 hours 24 minutes to polish off Isner.

Nadal dismissed Roddick in 1:53.

Indeed, Nadal’s superiority — managing to bludgeon Roddick with pinpoint precision — hushed the capacity crowd that appeared primed to cheer on the lone remaining American underdog.

But Roddick was never in the fight, even before he so visibly ran out of gas. Boasting a booming serve that once was deemed un-returnable, Roddick was broken in his first two service games to fall behind 4-0.

And the forehand that once pulverized opponents proved nothing more than ordinary to Nadal, who finished with 22 forehand winners to Roddick’s zero.

It was clear midway through the second set that Roddick was ailing, in addition to getting outplayed. He had no explosiveness in his legs. And he called for the trainer after getting broken a fifth time.

Still, Roddick played on, believing it unsporting to retire in a Grand Slam match — or any match — unless he risked doing physical harm to himself by continuing.

“I have seen a lot of guys this week just kind of bag,” Roddick said, referring to the record 15 mid-match retirements by players who were trailing. “You play till the end, in my mind.”

Tournament officials on Friday tweaked the schedule for Saturday’s women’s semifinals yet again.

The more anticipated clash, pitting No. 1 seed Caroline Wozniacki against three-time champion Serena Williams, will be played at 8 p.m. on 23,771-seat Arthur Ashe Stadium to capitalize on the CBS prime-time broadcast window.

The other semifinal, with ninth-seeded Samantha Stosur taking on unseeded Angelique Kerber of Germany, will be held at 6 p.m. on the 6,106-seat Grandstand Court because 10,103-seat Louis Armstrong Stadium remained out of commission because of rain water bubbling onto the court from below.

Also Friday, American wild-cards Jack Sock, 18, and Melanie Oudin, 19, won the mixed-doubles title with a 7-6 (7-4), 4-6, 10-8 upset of eighth-seeded Gisela Dulko and Eduardo Schwank.