Novak Djokovic fended off a fading Andy Murray 7-6 (1), 6-7 (1), 6-2, 6-4 in a matchup of past U.S. Open champions to reach the tournament's semifinals for the eighth consecutive year.

It took a while for the No. 1-ranked and No. 1-seeded Djokovic to push himself out front in a well-played, back-and-forth, three-hour, 32-minute match that ended after 1 a.m. Thursday in New York.

Djokovic broke the eighth-seeded Murray to go up 3-1 in the third set, then fended off a pair of break points in the next game. On the first, Murray sailed a backhand long to end a 28-stroke point, then leaned over and put a hand on his knee. On the second, he dumped a forehand into the net, then slammed his racket against his right thigh and yelled.

Soon, Murray was turning to his box to say, "Nothing in the legs." In the fourth set, a trainer came out to deliver a heat pack to Murray.

He had back surgery a year ago, and in his first-round match in New York last week, he barely managed to overcome cramps all over his body. Murray had looked fine since then, but he couldn't sustain his top form throughout the physically demanding quarterfinal against Djokovic, who won the U.S. Open in 2011 and has played in the past four finals.

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Novak Djokovic celebrates after defeating Andy Murray in their men's singles quarter-final match at the U.S. Open in New York on Wednesday night. The top-ranked Djokovic prevailed 7-6, 6-7, 6-2, 6-4. (Matthew Stockman/Getty Images)

On Saturday, Djokovic will take on 10th-seeded Kei Nishikori, the first man from Japan to reach the U.S. Open semifinals since Ichiya Kumagae in 1918. Nishikori outlasted third-seeded Stan Wawrinka of Switzerland 3-6, 7-5, 7-6 (7), 6-7 (5), 6-4 earlier Wednesday.

That match lasted more than four hours, and Nishikori managed to shake off any lingering exhaustion from his previous victory, which took 4:19 and ended at 2:26 a.m. ET Tuesday, matching the latest finish in tournament history.

Serena Williams secures semifinal berth

After a bad-as-can-be start, dropping the first three games, Serena Williams quickly turned things around and stretched her U.S. Open winning streak to 19 matches to get back to the semifinals.

Considered the best server in women's tennis, the No. 1-seeded Williams was broken twice in a row at the outset Wednesday night, before taking complete control for a 6-3, 6-2 victory over 11th-seeded Flavia Pennetta of Italy.

Williams is bidding to become the first woman with three consecutive U.S. Open titles since Chris Evert took four in a row from 1975-78. The 32-year-old American also is trying to pull even with Evert and Martina Navratilova at 18 Grand Slam singles trophies.

Williams, a five-time champion at Flushing Meadows, had not yet reached a major semifinal in 2014, bowing out in the fourth round at the Australian Open, the second round at the French Open, and the third round at Wimbledon. The last time she didn't reach at least one Grand Slam title match in a season was 2006, when she entered only two of the sport's top tournaments.

On Friday, Williams will meet Ekaterina Makarova, a Russian seeded 17th who advanced to her first Grand Slam semifinal by eliminating Victoria Azarenka 6-4, 6-2.

The other women's semifinal will be No. 10 Caroline Wozniacki of Denmark against unseeded Peng Shuai of China.

Makarova onto 1st Grand Slam semi 

Makarova reached her first Grand Slam semifinal, beating Victoria Azarenka in straight sets Wednesday.

The 26-year-old Russian won 6-4, 6-2 after losing her previous four major quarter-finals.

"I'm feeling amazing," she said. "Finally, I'm in a semifinal."

Azarenka acknowledged she suffered from food poisoning the day before, but didn't want to talk about how it might have affected her. Unusually subdued for most of the match, she smashed her racquet after one of her 27 unforced errors gave Makarova a break and a 4-2 lead in the second set.

"I'm not going to make any excuses," she said. "I did the best I could today.

"I want to give full credit to my opponent. She deserves to win. She played much better than me today."

The players were 16th and 17th in the seedings, but came in with very different resumes. Azarenka is a two-time Australian Open champion who lost to Serena Williams in the last two U.S. Open finals.

Yet in some ways, falling short of the semifinals Wednesday would have been more distressing for Makarova, who lost to Lucie Safarova in straight sets in the Wimbledon quarters this summer.

When she arrived at Flushing Meadows, Azarenka had played just eight matches since the Australian Open because of foot and knee injuries, her ranking plunging. She got to take the court five times here, a huge help to rediscovering her rhythm.

"I can take positive from this tournament," Azarenka said. "Two months ago, I didn't even think that I was going to be able to play."

But she had often looked shaky against qualifier Aleksandra Krunic in the fourth round before eking out a three-set victory, and on Wednesday, Makarova took full advantage of Azarenka's mistakes.

Makarova was coming off a straight-set upset of Wimbledon runner-up Eugenie Bouchard. Against Azarenka, the lefty's deep groundstrokes kept on the pressure.

Down an early break in the first set, Makarova immediately broke back and looked sharp the rest of the way. She has yet to drop a set at Flushing Meadows.

Her semifinal opponent could be Williams. The two-time defending champ faces 11th-seeded Flavia Pennetta to open the night session at Arthur Ashe Stadium.

Novak Djokovic and Andy Murray take the court after that for a rematch of the 2012 U.S. Open final. Stan Wawrinka was playing Kei Nishikori in the other men's quarter-final Wednesday afternoon.

Nishikori makes Japanese history

Kei Nishikori became the first man from Japan to reach the U.S. Open semifinals in 96 years, outlasting third-seeded Stan Wawrinka of Switzerland 3-6, 7-5, 7-6 (7), 6-7 (5), 6-4.

The match went four hours 15 minutes, and the 10th-seeded Nishikori managed to shake off any lingering exhaustion from his previous victory, which lasted 4:19 and ended at 2:26 a.m. Tuesday, matching the latest finish in tournament history.

Nishikori began slowly against the Australian Open champion, but eventually got his bearings and used crisp returns and strong net play to edge ahead. In Saturday's semifinals, Nishikori will face No. 1 Novak Djokovic or No. 8 Andy Murray, who each owns a U.S. Open title.