The 2021 US Open champion took only 22 minutes to sweep the first set 6-0 against Slovakian qualifier Viktoria Kusmova but faltered and lost the second set 7-5.
Raducanu summoned the trainer courtside to heavily strap her left ankle in a long injury break.
The 20-year-old Raducanu attempted to play on but was not able to complete the first point of the third set.
She was tearful when she came to the net and acknowledged she could not continue.
Raducanu was marked as one of tennis’ hottest stars when she won at Flushing Meadows but her career since has been dogged by injuries.
She retired from matches four times in 2022 and most recently has had to contend with a wrist injury.