The move came after a court annulled her diplomatic immunity in July.
"I can confirm that a warrant for the arrest of Grace Mugabe was issued last Thursday," police spokesman Vishnu Naidoo was quoted as saying by ZWNews on Wednesday.
He said the police were seeking the assistance of Interpol to enforce the warrant.
South Africa's government was criticised for letting Grace Mugabe, 53, leave the country after the alleged assault.
Gabriella Engels accused the former First Lady of beating the "hell out of me" with an electric extension cord in a hotel room in Johannesburg in August 2017. Pictures on social media appeared to show Engels bleeding from the head after the alleged assault.
Grace Mugabe said at the time that she had acted in self-defence after the "intoxicated and unhinged" model attacked her in the room where her two sons lived.
She had been jockeying to become Zimbabwe's next President until her husband, Robert Mugabe, was deposed in the military takeover in 2017 after 37 years in power.
It was unclear why the reporting of the warrant was delayed and there was no response from Grace Mugabe or Zimbabwean authorities.
Lobby group AfriForum, which had been pursuing the case, welcomed the arrest warrant.
"It seems that justice is going to take place and we are looking forward to this matter going forward," South Africa's Times Live website quoted AfriForum CEO Kallie Kriel as saying.
(With inputs from agencies.)