Madison Keys retired from her third-round clash with France's Alize Cornet early in the second set on Saturday with a neck injury.
The seventh seed was trailing 7-6(4) 3-2 when she shook her head and told the Frenchwoman and the umpire she could not continue.
The 25-year-old American, a 2017 finalist at Flushing Meadows, had a medical timeout between sets and called for assistance again during the second, where the trainer massaged her neck and shoulder.
- US Open 2020 live text commentary
- US Open 2020 order of play and schedule
- US Open 2020 results and scores
Keys struggled to raise her arms above her shoulder during the second set and grimaced every time she hit the ball, calling it quits after Cornet held serve to take a 3-2 lead.
Cornet said she could see Keys was hurting.
"I could see at the start of the second set that she was in real pain and she is not the type of girl who retires easily so she must have been in real pain," she added.
I am sorry for her.
Cornet added that when she saw Keys tighten up she knew that she had an opportunity to advance to the fourth round for the first time in New York and had to control her emotions.
"It was awful," Cornet said. "I got so tight because I could see that she could not serve normally ... (and) that I had a chance to break her and I shouldn't let the opportunity pass."
US Open: Serena Williams favourite to win record-equalling Slam
Cornet faces Tsvetana Pironkova in the fourth round after the Bulgarian recorded a 6-4 6-1 win over Croatia's 18th-seed Donna Vekic.
Additional reporting from Reuters