The story begins as Ali (then known as Cassius Clay) trains for his first title fight against Sonny Liston. He is considered the underdog, but he wins the fight and is crowned heavyweight champion. "I am the greatest", boasts the boxer, and the world begins to believe it.
Accepting the teachings of Islam, he discards his "slave name" and becomes Muhammad Ali. In the decade that follows, the film tracks the effects that his faith, political convictions and relationships have on his life. One of those relationships is with black activist, Malcolm X (Mario Van Peebles), and on a lighter level, is his friendship with well-known sports commentator of the period, Howard Cosell played by a virtually unidentifiable Jon Voight. Ali's weakness for women is not glossed over and Jada Pinkett Smith, Nona Gaye and Michael Michele drift in and out of the picture as his first three wives.
This is also the decade of the Vietnam War and Ali's refusal to be drafted into the army because of his religious beliefs and his subsequent banning from boxing test the extent of his convictions. Rather than fight a war he does not believe in, he risks his career and for three years he is inactive. The movie however, moves on to a final triumphant note for Ali when he regains his heavyweight title from the new world champion,George Foreman in Zaire, the event that became known as "Rumble in the Jungle".