The team said the search for a replacement will begin immediately.
The Lakers went 27-55 this past season, the second worst record in the Western Conference.
D'Antoni was hired on Nov. 12, 2012, replacing Mike Brown after he was fired when the team got off to a 1–4 start to the season.
According to Yahoo! Sports' Marc Spears, D'Antoni wanted his option for the Lakers exercised for the 2015-16 season and the team refused, which led to D'Antoni resigning.
“Given the circumstances, I don’t know that anybody could have done a better job than Mike did the past two seasons,” said Lakers general manager Mitch Kupchak. “On behalf of the Lakers, we thank Mike for the work ethic, professionalism and positive attitude that he brought to the team every day. We wish him the best of luck.”