Police spokesman Vishnu Naidoo said it related to an alleged attack in the upmarket Johannesburg neighbourhood of Sandton last year.
“I can confirm that a warrant for the arrest of Grace Mugabe was issued last Thursday,” Mr Naidoo said, adding that South African police were seeking Interpol’s help to enforce the warrant.
There was no immediate comment from Ms Mugabe or from authorities in Harare.
Last summer Ms Mugabe was accused of whipping a South African model in a Johannesburg hotel room, but the country granted her diplomatic immunity.
That immunity was overturned by a South African court this year after the alleged victim, Gabriella Engels, challenged the decision.
The 53-year-old had been jockeying to become Zimbabwe’s next president until her husband, Robert Mugabe, was deposed in 2017 after nearly four decades of rule.
She has since retreated from the public eye, and has denied assaulting Ms Engels. She has claimed the “intoxicated and unhinged” model attacked her first with a knife, which Ms Engels’ representatives AfriForum dismissed as a lie.
Additional reporting by Reuters
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