NEW YORK — There will be no U.S. Open matchup between Roger Federer and Rafael Nadal this year.

Federer’s 18-match Grand Slam winning streak ended with a 7-5, 3-6, 7-6 (8), 6-4 quarterfinal loss to Juan Martin del Potro on Wednesday night.

The result prevented Federer and Nadal from meeting in the semifinals, which would have been their first head-to-head showdown at Flushing Meadows.

It’s the only major tournament where the longtime rivals have never faced each other.

Instead, it will be 2009 champion del Potro against two-time winner Nadal in Friday’s semifinals.

The other semifinal is Pablo Carreno Busta against Kevin Anderson.

Nadal was honest as can be before the U.S. Open when asked whether he hoped to face Federer in the semifinals.

The answer, the No. 1-seeded Nadal said, was no – because he’d rather go up against someone easier to beat.

Well, Nadal did his part to make such a matchup a possibility, overwhelming 19-year-old Russian Andrey Rublev 6-1, 6-2, 6-2 in the quarterfinals

In the women’s quarterfinals, 15th-seeded Madison Keys completed an all-American lineup in the final four with a dominating 6-3, 6-3 victory over 418th-ranked qualifier Kaia Kanepi of Estonia in only 69 minutes. Earlier, No. 20 CoCo Vandeweghe knocked off top-seeded Karolina Pliskova 7-6 (4), 6-3. Keys and Vandeweghe will meet Thursday to determine which reaches her first Grand Slam final.

Venus Williams and Sloane Stephens set up their all-U.S. semifinal with victories Tuesday.

It is the first time since 1981 that all four women’s semifinalists in New York are from the host country.

While Federer entered Wednesday night’s match with a 16-5 head-to-head mark against del Potro, the big-hitting Argentine won his only Grand Slam trophy with a five-set victory in the 2009 title match at Flushing Meadows.

The expectation, certainly, was their quarterfinal this time would be more competitive than Nadal’s stroll past the 53rd-ranked Rublev, which barely lasted more than 1½ hours.

“He gave me a lesson,” acknowledged Rublev, the youngest U.S. Open quarterfinalist since Andy Roddick in 2001.

Rublev didn’t put up much of a fight, with seven double-faults among his 43 unforced errors.

“I will try now to practice harder to improve everything for the next time if we play each other,” Rublev said, “to try to compete better.”

Truth is, the way Nadal is playing at the moment, few would be able to offer much in the way of a challenge.

He has won his past three matches in straight sets, his uppercut of a forehand at its most dangerous best.

“He’s been playing better and better every day,” Moya said. “The last couple of matches have been very good. He is confident. He had a few doubts at the beginning of the tournament that I believe now are gone and he is able to play his best tennis.”