“Jada, can’t wait for GI Jane 2,” he said, in an apparent reference to her shaved hairdo – which is a result of the hair loss condition alopecia.
Smith walked on stage and struck Rock before returning to his seat and shouting: “Keep my wife’s name out of your [expletive] mouth.”
He later apologised on stage.
“I want to apologise to the Academy. I want to apologise to my all my fellow nominees,” he said during a tearful acceptance speech for best actor.
The star picked up the first Oscar of his career for playing the father of tennis legends Venus and Serena Williams in King Richard.
“Art imitates life. I look like the crazy father, just like they said about Richard Williams. But love will make you do crazy things.”
Rock’s joke referred to 1997 film GI Jane, in which Demi Moore played the title role with a severe buzzcut.
The comedian looked stunned in the immediate aftermath of the incident, but told the audience: “That was the greatest night in the history of television.”
He then handed over the best documentary prize, which was the reason he was on stage.