Stung by dropping the first set to an unseeded opponent, top-seeded Rafael Nadal swept imperiously through the next three to beat Mardy Fish on Wednesday and reach the semifinals of the U.S. Open for the first time.

Forced to wait until 11.30 p.m. local time for his match to start, and surprised by the spirited start by the American in front of his home crowd, Nadal dominated thereafter to set up a semifinal against Andy Murray.

The sixth-seeded Scot prevailed earlier in a tight struggle with Juan Martin del Potro, beating the Argentine 7-6 (2), 7-6 (1), 4-6, 7-5 to reach his first grand slam semifinal.

In the women's draw, Serena Williams rallied from a break down in both sets to edge big sister Venus 7-6 (6), 7-6 (7), while Russian Dinara Safina comfortably beat Italian Flavia Pennetta 6-2, 6-3.

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Nadal, who has won four titles at the French Open and one at Wimbledon and had usurped Roger Federer as the world's No. 1 player ahead of this final grand slam of the year.

Fish took the opening set on the strength of a 23-6 edge in winners and one service break, but the powerful Spaniard never faced a break point the rest of the way.

Murray ousted del Potro, who had never advanced farther than the third round in a grand slam before. The Argentine had never won a tournament before July, then ripped off four straight titles to soar up the rankings. His run of wins on tour was second only to Nadal.

Murray, playing in the quarterfinals for a second straight Grand Slam tournament, repeatedly won points with drop shots. His ranking, already a career high, will now climb to No. 4, matching the highest ever for a British man in the rankings' 35-year history.

Murray's nerves showed at times. Serving for the second set, he lost the game at love. But he loosened back up to easily win the tiebreaker.

The Scot was up a break in the third and the match seemed close to over. But a string of mistakes by Murray seemed to revive del Potro, who had his knee strapped during the match, and he forced it to a fourth set.

Fourth-seeded Serena Williams barely got the better Venus Williams in quarterfinal that was fit for a final, coming back to win and go one up in their head-to-head history.

Serena trailed 5-3 in both sets and faced set points in both — a total of 10, including eight in the second. But she advanced to the semifinals at Flushing Meadows for the first time since 2002, the year she won her second U.S. Open.

"I felt like I was always in control," Venus said. "If it was someone else, I definitely feel like I would have won the match."

In the semifinals, Serena will meet No. 6 Safina, who advanced earlier in the day by overpowering No. 16 Pennetta. The No. 2 and title favorite Jelena Jankovic will face No. 5 Elena Dementieva in Friday's other semifinal.

The seventh-seeded Venus had all sorts of chances to take control. In the second tiebreaker she could not convert on four set points.

"I'm a very good closer," Venus said, "I've never had a match like this in my life, so I guess there's always a first."

In contrast, when Serena earned her first match point she converted it, when the Venus ended an 11-stroke exchange by missing a forehand.

"It was really luck for me, because she never makes those errors," Serena said.

Down 6-4 in the opening tiebreaker, Serena reeled off four points in a row, saving two sets points and ending it when Venus pulled a forehand wide after a 10-stroke exchange.

Safina rolled off her powerful service to dominate Pennetta. She won 83 per cent of points when she got her first serve in play. The Russian's low error rate and powerful groundstrokes will make her a difficult opponent for Serena. The American has won three of their five previous meetings.