Blockx stopped playing in the third set because of injuries to his leg, ribs and back, sending Khachanov to his third grand slam semi-final.
"I think my body just gave up," Blockx said.
Khachanov won the first two sets 6-2 and 7-5, and the No.28 seed from Belgium decided it was time to stop after Khachanov broke his serve to take a 3-2 lead in the third.
"It's not easy really to play because from one side I was feeling I was dominating from the beginning, then I started to feel like he was struggling more and more," Khachanov said, adding he saw Blockx was "suffering all over his body."
Khachanov will play top seed Alexander Zverev who took another big step towards a second grand slam title by beating Dutchman Botic van de Zandschulp 6-2 7-5 6-1. The Russian got to the semi-finals of the US Open in 2022 and the Australian Open in 2023.
Khachanov was unseeded in a grand slam tournament for the first time since 2018 after a strange season. He reached at least the third round of all four majors for the first time but is just 10-15 in other events, with losses in the opening rounds of all three hard-court events before coming to New York.
Blockx said he nearly stopped in his last match because of his injuries. As he got treatment for multiple body parts on Wednesday, he said he was neither upset nor angry.
"To be honest, during the match, it was quite funny to me. I just had to laugh it off, because it was just something new the whole time," he said.
"I think it was just my body that started compensating as well. I was starting to do different motions than I usually do just to avoid the pain."
The French Open champion and Wimbledon runner-up will play Friday against Khachanov, while Americans Ben Shelton and Frances Tiafoe meet in the other semi-final.
Zverev became the first men's No.1 seed to play five-set matches in each of the first two rounds of a major in the Open era, which began in 1968. But he won his last three matches in straight sets and is the only man to reach all four major semis this year.
After playing more than 4 1/2 hours in each of the first two rounds, Zverev hasn't been on the court more than 2 1/2 in his last three matches.
"In other tournaments I would have been out in the first round but here I can fight back and play best-of-five, play 4 1/2 hours and somehow win the match and somehow get into the tournament," Zverev said.
"And then I start playing better throughout the tournament and definitely happy to be in the semi-finals here, but of course I want to go further."
He went to the final in 2020 but blew a two-set lead against Dominic Thiem. That was the closest he would come to a major title until his victory this year at Roland Garros and the German now is 23-2 in grand slams this season.
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