David Rubin, president of the academy, confirmed Smith's resignation in a statement and said a disciplinary inquiry into the assault would continue to move forward.
"We have received and accepted Mr. Will Smith's immediate resignation from the Academy of Motion Picture Arts and Sciences," Rubin said. "We will continue to move forward with our disciplinary proceedings against Mr. Smith for violations of the Academy's Standards of Conduct, in advance of our scheduled board meeting on April 18."
The academy said in a previous statement that Smith could face suspension, expulsion, or other sanctions as a result of its inquiry into the incident.
The attack occurred after Rock joked about Smith's wife Jada Pinkett Smith's bald head, referring to the film G.I. Jane. Smith returned to his seat after slapping Rock and later received his first Oscar for his portrayal of Richard Williams in King Richard.
On Friday, Will Packer, producer for the Oscars show, told Good Morning America the academy was on the verge of physically removing Smith from the ceremony after the attack. Instead, one of the producers stepped forward and said that Rock did not want to "make a bad situation worse."
Smith announced his decision to resign from the academy in a statement obtained by Variety, in which he apologized to Rock, the academy, and the other nominees and winners of the ceremony.
"The list of those I hurt is long and includes Chris, his family, many of my dear friends and loved ones, all those in attendance, and global audiences at home," Smith said, according to the statement. "I betrayed the trust of the Academy. I deprived other nominees and winners of their opportunity to celebrate and be celebrated for their extraordinary work. I am heartbroken."