The 38-year-old heavyweight champion made the announcement at a news conference, putting to rest any speculation about a rematch with Vitali Klitschko, whom he beat in his last fight last June.
Lewis was told by the World Boxing Council he must agree to face the Ukrainian again by March 1 or be stripped of his title.
The Telegraph reported Lewis had been considering his future for some time, and it is believed his mother, Violet, ultimately had the biggest say in his decision to quit.
Lewis becomes the first reigning heavyweight champion to retire since Rocky Marciano in 1956.
Lewis' 14-year career began after he claimed the Olympic super-heavyweight title in 1988 while representing Canada. He lost only two of his 44 paid fights, against Oliver McCall and Hasim Rahman -- both defeats he later avenged.
Lewis went on to wipe out Mike Tyson in the eighth round in Memphis in 2002 and was urged to retire on top, but instead battled Klitschko and retained his title when the Ukrainian was forced to retire with bad cuts.