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NEW YORK—Darting all over the court, Andy Murray has made running strikes look as routine as rally shots during the first week of the U.S. Open.

Bouncing inside the baseline, Novak Djokovic has been busy taking shots on the rise—and dancing with fans in celebration after sending opponents packing.

These former U.S. Open champions have high-stepped into a quarterfinal that popped off the page when the draw was announced. Djokovic and Murray were born a week apart, grew into junior rivals, and made the most of all that roaming room in Arthur Ashe Stadium that last time they ran into each other in New York. They turned the largest Grand Slam stadium in the world into a block party of sprinting exchanges spilling well beyond the lines as Murray won his maiden major in a five-set 2012 U.S. Open final.

Wimbledon winner Djokovic has danced into his 22nd consecutive Grand Slam quarterfinal barely missing a beat—and without dropping a set. Maybe Djokovic is determined to minimize the draining effect that going the distance took on his body in Grand Slam finals last year—he looked depleted in losing at Wimbledon and the U.S. Open after winning grueling, five-set semis. Perhaps coach Boris Becker is urging him to play inside the baseline to assert his speed and athleticism offensively, or maybe it's just been so brutally hot Djokovic is in a hurry to escape the swelter. Regardless of reason, the top seed is getting off first in rallies.

U.S. Open Quarterfinal Preview: Novak Djokovic vs. Andy Murray

U.S. Open Quarterfinal Preview: Novak Djokovic vs. Andy Murray

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"I want to use the first shot more efficiently," said Djokovic, who has dropped serve four times in four matches. "I want to be more aggressive the first shot after the serve and after the return. I want to try to get into the court and dominate the rally, dominate the play. That's the goal."

It's a goal he executed while beating Murray, 7-5, 6-3, in their most recent meeting in the Miami quarterfinals this spring. Djokovic served 72 percent, hit seven aces, and won 55 percent of his second-serve points in that match. He will try to impose that first-strike approach in the rematch. The question is: How will Murray, who is sometimes too content to rely on his speed and play a passive-aggressive, counter-punching style, respond? Murray's sliding first serve and his tricky slice backhand can be stinging shots on the fast hard court and he's highly skilled around the net—though often averse to applying those attacking skills.

Though he appeared on the verge of cramping and retching a few times in the first week, the No. 8 seed knows he can go the distance with Djokovic because he outlasted the elastic Serbian here two years ago for the title, 7-6 (10), 7-5, 2-6, 3-6, 6-2. He also knows he can take charge of rallies because he did it in a straight-sets win over Djokovic in the Wimbledon final last year.

Less than a year removed from back surgery, Murray has not played his best tennis, but he has the variety of shot and court sense to gunk up the gears in Djokovic's well-oiled game. Does the ornery Scot have the self-belief and daring to pull it off and salvage a disappointing season?

U.S. Open Quarterfinal Preview: Novak Djokovic vs. Andy Murray

U.S. Open Quarterfinal Preview: Novak Djokovic vs. Andy Murray

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"I don't feel like I'm that far away from playing my best tennis," said Murray, who has won the opening set in all eight of his career wins over Djokovic. "It's still obviously a long way from trying to win the tournament, but it's only nine sets now, three matches, and just try and take it one set at a time. [I am] maybe five, six days away from potentially winning another Grand Slam. I know there is a lot of work to be done between now and then. But putting everything out there on the courts, last Slam of the year, hope I can play well."

Ultimately, Djokovic's forehand from the center of the court is more dangerous, he typically hits his second serve with a bit more bite, and he has played sharper tennis throughout the tournament. Since falling in the 2012 Flushing Meadows final, Nole has beaten Andy in four of their last five meetings—though the one loss was massive.

Murray is one of the few men in the world who can run with Djokovic in physical, best-of-five-set matches, but the world No. 1 looks fresher and typically plays with more margin on his shots—all assets amid the swirl and swelter of Ashe Stadium.

Pagliaro's Pick: Djokovic in four sets