After the alleged assault with an electric cable came to light in August 2017, the South African government granted Grace Mugabe diplomatic immunity.
That immunity was overturned by a South African court this year after the alleged victim, model Gabriella Engels, challenged the decision.
"I can confirm that a warrant for the arrest of Grace Mugabe was issued last Thursday," South African Police Service spokesman Vishnu Naidoo said, adding that police were seeking Interpol's help to enforce the warrant.
There was no immediate comment from Mrs Mugabe or from authorities in Harare.
Mrs Mugabe was seen as a potential successor to her 94-year-old husband Robert, who ruled Zimbabwe from 1980 until he was ousted in a coup late last year, at the time of the incident in a luxury hotel in Johannesburg's Sandton district.
She has denied assaulting Engels with an electric cable, saying an "intoxicated and unhinged" Engels attacked her with a knife after the model had gone to see the Mugabes' sons at the hotel.
South African advocacy group Afriforum, which represented Engels, has dismissed Mrs Mugabe's denial as a lie.
Mrs Mugabe has retreated from the limelight in Zimbabwe since her husband was ousted in the November 2017 coup. (Reporting by Alexander Winning in Johannesburg and MacDonald Dzirutwe in Harare Editing by James Macharia)
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