D'Antoni was hired by the Lakers to replace Mike Brown in November, 2012. Under his guidance, the Lakers posted a 67-87 record.
"Given the circumstances, I don't know that anybody could have done a better job than Mike did the past two seasons," Lakers General Manager Mitch Kupchak said.
"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."
The 62-year-old D'Antoni still had one year remaining on his contract with the Lakers but there had been growing speculation about his position with the battling team.
The Lakers finished the 2013-14 season a dismal 27-55, the worst 82-game record in the team's history and his departure was welcomed by some of his critics.
"Happy days are here again. Mike D'Antoni resigns as Lakers coach. I couldn't be happier," former Lakers great Magic Johnson tweeted.
D'Antoni had previously served as head coach of the Denver Nuggets, Phoenix Suns and New York Knicks.
He was named NBA coach of the year for the 2004-05 season and has a career record of 455-426.
A proponent of the fast-break and up-tempo offense, D'Antoni's style never really worked with a Lakers roster that was plagued by injuries to key players, including Kobe Bryant, who managed just six games this season.
D'Antoni is the fourth head coach to leave the Lakers, one of the NBA's most historically successful franchises, in the last three years.
In his statement, Kupchak said the search for a replacement would begin immediately although no timetable had been established.
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- Mitch Kupchak
- Mike Brown