NEW YORK -- Betrayed by his 38-year-old body -- and his forehand -- Roger Federer is done at the US Open.

Federer's upper back and neck gave him trouble, he kept missing makeable shots and he kept giving away the lead against a guy he'd never lost to. It all added up to getting beaten 3-6, 6-4, 3-6, 6-4, 6-2 by 78th-ranked Grigor Dimitrov in the quarterfinals before a stunned crowd at Arthur Ashe Stadium on Tuesday night.

"Grigor was able to put me away,'' Federer said. "I fought with what I had.''

Chasing a 21st Grand Slam title, and sixth at Flushing Meadows, Federer appeared to be flexing his upper back after some points and said afterward that he began feeling something in that area in the afternoon.

He took a rare-for-him medical timeout after the fourth set, leaving the court with a trainer. When play resumed after a break of nearly 10 minutes, Federer's form never picked up.

"He started slowing down a little bit,'' Dimitrov said. "For sure, in the end, he was not 100% of himself.''

Federer kept contributing to Dimitrov's cause, missing shots this way and that, long or wide or into the net.

The stats were staggering and showed exactly how off Federer was on this evening: 61 unforced errors, 33 on the forehand side. Compare that to his 40 total winners.

And so his two-sets-to-one lead vanished.

"Start of the fourth wasn't ideal,'' Federer said. "Start of the fifth wasn't ideal.''

Federer had been 7-0 in their head-to-head series, taking 16 of the previous 18 sets against Dimitrov, who is a decade younger and long ago was dubbed "Baby Fed'' because of his similar one-handed backhand and all-court game.

Federer is now 43-2 in his US Open career against players ranked outside the ATP's top 50. His other loss came last year in the round of 16, against the 55th-ranked John Millman.

The No. 3-seeded Federer could have become the oldest man to reach a Grand Slam semifinal since Jimmy Connors was 39 in 1991 at the US Open. He could have claimed a berth in his record 56th career major semifinal.

"Just disappointed it's over, because I did feel like I was actually playing really well after a couple of rocky starts,'' Federer said. "It's just a missed opportunity, to some extent.''

He joins Novak Djokovic on the sideline less than two months after their epic five-set Wimbledon final. Defending US Open champion and No. 1 seed Djokovic retired from his fourth-round match in New York because of a painful left shoulder.

That leaves No. 2 Rafael Nadal as the only member of the Big Three still in the draw.

Dimitrov will participate in a Slam final four for the third time, facing No. 5 seed Daniil Medvedev on Friday.

Dimitrov has struggled for much of 2019, failing to even get to a quarterfinal anywhere since Week 1 of the season. And it's been nearly 1½ years since Dimitrov reached a semifinal at any tour-level event, let alone a major.

His Grand Slam results have been trending in the wrong direction, too, from a loss in the fourth round at the Australian Open to the third round at the French Open to the first round at Wimbledon.

So his ranking, as high as No. 3 a couple of years ago, is nowhere near that now. His coaches, Andre Agassi and Radek Stepanek, aren't anywhere near Flushing Meadows, either.

They opted to stay away from the tournament. Asked why, Dimitrov hemmed and hawed.

It's certainly working so far, as Dimitrov became the lowest-ranked US Open semifinalist on the men's side since the aforementioned Connors run in 1991, when he was ranked No. 174.

The Associated Press contributed to this report.