The Polish world No. 1 was stunned 2-6, 4-6 by the sixth-seeded American, who was more consistent, served better and made fewer mistakes.
The Polish tennis ace, meanwhile, committed 41 unforced errors, nearly twice as many as her opponent, Poland's PAP news agency reported.
She was sent packing at Flushing Meadows in one hour and 28 minutes, it said.
The 23-year-old Pole, who won the US Open in 2022, was aiming for her sixth Grand Slam singles title this year in New York.
She was the last Pole remaining at the 2024 US Open, which runs until Sunday.
(gs)
Source: IAR, PAP