(CNN) In their long and storied careers, Roger Federer and Rafael Nadal have never played against each other in the US Open.

And it won't happen this year, either.

Juan Martin del Potro, who stunned Federer in five sets in the 2009 US Open final for his only major title, took the rematch as well, winning 7-5, 3-6, 7-6(8), 6-4 Wednesday night at Arthur Ashe Stadium in Flushing, New York.

Del Potro, seeded 24th, reaches his first major semifinal since 2013 at Wimbledon. He will face No. 1 Nadal -- who keeps the top spot with Federer's loss -- next, while the other semifinal pits No. 12 seed Pablo Carreno Busta of Spain against No. 28 Kevin Anderson of South Africa.

"I think I played my best match of the tournament," del Potro said in his on-court interview. "I did everything well. I served so good. I hit my forehand as hard as I can. I think we played a great match, and I deserved to win in the end."

Del Potro and Federer.

It's the second time the Argentine, now 28, prevented a Nadal-Federer clash in New York. In 2009, del Potro defeated Nadal in straight sets in the semifinal en route to facing Federer in the final.

"Hopefully I can repeat the result," del Potro said of his upcoming rematch with the 31-year-old Spaniard.

Federer-Nadal US Open semifinal thwarted

Nadal did his part on Wednesday, dispatching 19-year-old Russian Andrey Rublev 6-1, 6-2, 6-2 in the afternoon quarterfinal. Prior to the start of del Potro's match, Nadal was asked about the possibility of playing him.

"Juan Martin is a top player, no?" Nadal said. "It's true that when he's playing well, it's difficult to stop him. Probably the forehand is maybe the fastest on the tour. And of course to win tonight, he should be serving well. If he serves well and hit well his forehand, he's a player that have the chance to win against, of course, everybody.

"If I play against him, of course I have to play my best tennis. I need to be very focused with my serve and play aggressive, because if you let him play from good positions with his forehand, you are dead, because he plays super-aggressive, hitting so hard."

To get to Nadal, No. 3 Federer, 36, had to get through del Potro first -- no easy task for the Swiss. The Argentine entered Wednesday 5-16 against Federer, but all of those wins were on hard courts, including coming back from a set and a break down to deny Federer a sixth consecutive US Open title in 2009.

Federer last won the US Open in 2008.

That moment eight years ago has been the biggest grand slam highlight for del Potro, who has undergone four wrist surgeries in his career.

"I cannot believe to play another semifinal after all my injuries, after all my surgeries," del Potro said. "Especially to play here in New York is great. It's my favorite tournament, my favorite city to play tennis."

The dream Federer-Nadal US Open matchup has almost happened a few times. In addition to 2009:

2008: Nadal lost to Andy Murray in the semis, who lost to Federer in the final.

2010: In the semifinal, Federer held two match points, but he still lost to Novak Djokovic. Djokovic went on to lose to Nadal in the final.

2011: Federer once again had two match points against Djokovic in the semifinal, but the Serb came through again, this time beating Nadal in the final.

2013: Federer bowed out in the fourth round to Tommy Robredo, who lost to eventual champion Nadal in the quarterfinals.

Del Potro: "Happy every time I play here"

In his previous match, a five-set win against No. 6 Dominic Thiem, del Potro, who lost the first two sets, contemplated retiring during the match. Del Potro said was ailing, saying he couldn't breathe or move well. But when he won the third set to stay alive, the crowd came to life, and it was one of the most energetic crowds seen at the second-year Grandstand court.

Wednesday's match at Ashe had a different vibe.

The first set lacked flair, as both players held serve until it was 5-5. A Federer double fault in the next game opened the door slightly for del Potro to break, and he comfortably served out the set.

In second set, Federer broke for a 3-1 lead and closed it the way his fans have been accustomed to seeing over the years.

Another Federer double fault -- this time on break point -- gave del Potro the early break in the third set. Del Potro later donated it back with a double of his own. The set went to a tiebreak, and Federer jumped to a 3-0 lead, but del Potro seized control late, winning it 10-8 for a two-set lead and generating a roar from the crowd.

The fourth set shifted del Potro's way when a Federer overhead smash attempt went into the net, setting up break point to give del Potro a 3-2 lead. The fans at Ashe eventually grew quiet.

On match point, a forehand winner, del Potro lifted his arms into the air in triumph.

"You make me feel happy every time I play here," del Potro said to the crowd. "I love your support, guys."