For Swiatek, 25, a fourth-round exit is a disappointing end to her Grand Slam season, with a quarter-final appearance at the Australian Open her best result.
She was beaten in round four of the French Open, while the defence of her Wimbledon title ended in the third round.
It means that, for the first time since 2021, Swiatek will end a year without winning one of the sport’s four majors.
Swiatek, who received treatment to her left thigh when leading 2-1 in the second set, had entered the US Open in excellent form by winning the WTA 1000 event in Toronto and getting to the semi-finals in Cincinnati, while she had progressed through to round four without dropping a set.
Reflecting on losing the first set to Zheng, Swiatek said she simply missed too many shots after going 5-0 up.
“My focus was the same as always,” said the six-time major winner. “I wanted to play the same as always. [I] just started to miss too much, wanted to adjust it, but nothing kind of worked at that point.
“I knew I was going to have another chance and I wanted to use it, but I missed them all.”
She continued: “I wouldn’t say it had anything to do with mentality. It was more that I started making mistakes from easy balls and Qinwen stopped doing mistakes. She played the balls better.”