As the opening credits roll, we hear Malcolm X (Denzel Washington) delivering a speech about the oppression of the white race against the black race, openly and loudly accusing whites of murder, rape and slavery. Intercut with the credits is footage of the 1991 beating of Rodney King by Los Angeles police officers and an American flag burning into an "X".
In the Roxbury neighborhood of Boston, in the early 1940s during World War II, a young Malcolm Little meets with his friend, Shorty (Spike Lee) at a local barber shop to have his hair straightened to make him acceptable to whites. The process is a painful one, with a concoction of eggs and lye applied to Malcolm's head and combed out. Malcolm admires himself in the mirror and he and Shorty take to the streets dressed in colorful "zoot" suits.
In a flashback sequence, Malcolm narrates that he grew up poor in rural Nebraska. When his mother was pregnant with him, a small group of Ku Klux Klan riders broke the windows of his parents' house, looking for his father, a local activist. Malcolm later narrates that his family's home was burned down and his father was murdered when he was four or five, thrown in front of a train after suffering a skull injury. The case was falsely recorded as a suicide and his family received no compensation, becoming destitute. Malcolm's mother, who was of Caribbean descent and partially white, married his father because he was black and a follower of Marcus Garvey, who preached that Black Americans should return to Africa to have their own region of the world, free of white influence. Eventually, his mother was remanded to a mental institution and Malcolm and his brothers and sisters became wards of the state. Malcolm, while in grade school, showed excellent academic skills and told a teacher he wanted to be a lawyer. However, his racist teacher tells him that it "isn't a practical career for a negro".
Flashing back to contemporary 1944, Malcolm and Shorty and their girlfriends go to a jitterbug club. After a rigorous dancing number, Malcolm meets Sophia (Kate Vernon), a white, blond woman who becomes infatuated with him. Malcolm's black girlfriend, Laura (Theresa Randle), is a devout Catholic and has avoided Malcolm's sexual advances. Eventually, Malcolm takes up with Sophia. At one point, he treats her with obvious racial misogyny, getting her to feed him breakfast.
Working for a local railroad company, Malcolm travels to Harlem. He goes to a bar where his drink is doubled unexpectedly by a man named West Indian Archie (Delroy Lindo), who runs numbers locally. When Malcolm is harassed by another patron who insults his clothes and speaks ill of his mother, Malcolm hits the man in the head with a liquor bottle. Archie recognizes that Malcolm won't back down in a fight and calls him over to his table. Malcolm sees immediately that Archie is a person of considerable influence and goes to work for him, running numbers.
One night, while Malcolm, Sophia and Archie drink and snort cocaine, Malcolm places a bet for several numbers with Archie. One of Malcolm's numbers hits and he stands to collect a large sum of money. Archie denies that Malcolm had the number and reminds his protege of his reputation for never forgetting a number. Malcolm chooses to break his ties with Archie.
A few nights later, at a dinner club, Archie threatens Malcolm. Malcolm escapes through the bathroom window. He returns to Boston, reconnects with Shorty and the two resolve to become petty thieves. One of their first partners, Rudy, tells them about a elderly man he takes care of who has money and many valuable items in his house. When Rudy declares he'll lead the group, Malcolm plays Russian Roulette, threatening to blow off Rudy's nose. A terrified Rudy tells Malcolm to lead the group.
The robbery is a success and over a period of time, Shorty and Malcolm loot a considerable amount. One night, while Shorty and Malcolm straighten Malcolm's hair, they discover the water has been turned off. Malcolm is forced to rinse his head in the toilet bowl and he and Shorty are arrested when the police burst in as well as their white girlfriends Sophia and Peg (Debi Mazar). The racist judge (a cameo by civil rights attorney William Kuntsler), after hearing a guilty verdict, sentences the two white women to 18 months for their association with the robbery group, but harshly sentences both Shorty and Malcolm to eight to ten years for 14 different robbery charges and declares the sentences will be served concurrently (a devastated Shorty faints in the courtroom, thinking he'd serve over 100 years until Malcolm explains what "concurrent" sentencing is).
Malcolm is sent to a Massachusetts penitentiary. On his first day he refuses to recite his incarceration number and is thrown into solitary confinement. The prison priest (Christopher Plummer) tries to reach Malcolm but is obscenely rebuffed. Malcolm is eventually released and recites his number. While in the showers, straightening his hair, he is met by Baines (Albert Hall), a member of the Nation of Islam, the black Muslim organization of the United States. Baines tells Malcolm that the best way out of prison, both the penitentiary and the figurative prisons of his mind, is through the teachings of Elijah Muhammad (Al Freeman Jr.), the founder and leader of the Nation of Islam. Malcolm refuses at first but grows more interested in Baines' preachings. Malcolm becomes a willing student; Baines tells him that all white people are not to be trusted. Baines has Malcolm copy out an entire English language dictionary, pointing out the double-standards that guide words like "black" and "white", telling his student that he must learn the meanings behind every word. Malcolm is reluctant at first to pray directly to Allah until he has a vision in his jail cell of Elijah Muhammad. Muhammad tells him that the only path to truth is through Allah. Malcolm finally gains the courage to pray as a Muslim. Malcolm also becomes a sore point for the prison priest; Malcolm challenges the traditional images of Jesus and the apostles, claiming they were anything but white.
Malcolm is paroled from prison in 1952, after serving six years and he goes to the Nation's headquarters in Chicago where he meets Elijah Muhammad himself. Malcolm is noticeably humbled by the experience and breaks down in awe-filled tears at meeting his savior. As part of joining the Nation of Islam, Elijah Muhammad instructs Malcolm to drop his last name of 'Little', which his ancestors inherited from a white slave owner, and replace it with the letter 'X' which is a symbol of his lost African surname.
Malcolm X returns to Harlem and begins his life as a preacher for the Nation of Islam. The Nation sets up a mosque in a single room and their congregation quickly grows. At one point, Malcolm, while preaching a sermon, sees Shorty in the crowd. He embraces him and the two go out for coffee. Shorty tries to get Malcolm to join him for a cocaine fix but Malcolm tells him that he's clean. Malcolm gets news about West Indian Archie and his old gang from Shorty and finds out where Archie is living. Archie has since suffered a stroke and lives as an invalid in a squalid Bronx apartment. Malcolm visits him and comforts him when he sees how poor life has become for his old boss. Malcolm also challenges the Harlem division of the New York City Police Department when one of his temple's members, Brother Johnson, is beaten in the streets and taken to jail and denied medical attention. Malcolm gathers the Fruit of Islam, the Nation's security force, and, joined by a growing mob of local protesters, marches on the police precinct, demanding to see Johnson. When he is turned down he calmly and firmly tells the officers in charge that neither he nor the Fruit of Islam will move. The silent protest works and Johnson is taken to the hospital. Malcolm orders the Fruit of Islam to disperse and leaves the angry crowd on the street for the police to deal with. As the Nation leaves, the captain remarks "that's too much power for one man to have."
In 1958, Malcolm meets his future wife, nurse Betty Sanders (Angela Bassett). The two are instantly attracted to each other and Malcolm eventually proposes to her. They are married in a private ceremony and plan to have children. They are soon the parents of four daughters.
Over the next few years as Malcolm's influence grows, he soon finds himself in a high advisory position to Elijah Muhammad himself, which draws much jealously from Baines. As a result, Malcolm receives less attention in the Nation's official publication, "Muhammad Speaks". Baines speaks to Muhammad directly, telling him that Malcolm may be shamelessly courting the white media for himself, rather than for the good of the Nation. Following a formal public speaking session, Malcolm is confronted by a disgruntled man who suggests that Muhammad may not be the benevolent leader the Nation believes him to be.
Malcolm, tipped by Betty, begins to investigate reports in the New York Post that Muhammad himself may have fathered illegitimate children with at least two unmarried women who served on his office staff. Malcolm talks to the women who confirm the reports and have been ostracized within the Nation. Malcolm privately confronts Muhammad who claims that, because he himself never married, that he must father his progeny any way he can. Baines also tries to justify Muhammad's philandering by recounting the stories of both Noah (a drunk) and Solomon (who had many wives). Malcolm is not convinced and loses much of his stature and faith in the Nation of Islam.
In November 1963, Malcolm's candid and brutally truthful reputation is further damaged when, following the assassination of President John F. Kennedy, publicly states that the president's death was an example of the historical violence of the white race and the United States itself, referring to the incident as an example of "the chickens coming home to roost." The remark is quickly misconstrued in American newspapers and Muhammad, who appears to be in poor health, suspends Malcolm's duties as the Nation of Islam's spokesperson for 90 days.
Malcolm decides to complete a "hajj", a holy journey of self-discovery to the Middle East and Mecca in Saudi Arabia, required of all Muslims if they are able. He tours the ancient pyramids at Giza, knowing that he's being tailed by two men he assumes are CIA agents. Arriving in Mecca, he participates in the Muslim ritual of the seven circuits around the Kaaba, drinking from the Well of Zamzam and kissing the Black Stone. He also realizes that Islam is not limited to people of Arab, Middle Eastern or African descent, but the many people in his pilgrimage include many Caucasian whites, mixed race people and Asians as well. Malcolm willingly eats and prays with them. The hajj changes Malcolm's outlook and he experiences a spiritual re-awakening, realizing that exclusion of races other than African-Americans from Islam cannot accomplish anything.
Returning to the United States in 1964, he gives a press conference where he declares that his days of preaching for African-American separation from white America are over. He forms a new Islamic organization, the Organization for African-American Unity (OAAU), one that will spread the word of tolerance of all who wish to worship Allah and the Qur'an, and which involves breaking his relations with the Nation of Islam. Very soon, Malcolm's family begins to receive death threats on the phone from Nation of Islam members. Malcolm guards his house at night with a rifle.
One night in February 1965, two firebombs are thrown at Malcolm's house and he gives a public statement to a television news crew that if he'd actually seen the bombers himself, he'd have opened fire on them in the street.
Malcolm receives further death threats and becomes somewhat despondent. He arranges to speak at the Audubon Ballroom in Harlem on February 21, 1965, his first such public speech since founding OAAU. Malcolm goes to a New York hotel and stays overnight there, possibly to draw attention away from his family. He receives more death threats from the Nation of Islam in his hotel room. He drives to the Audubon and meets a woman on the street who tells him not to listen to his detractors and that Jesus will protect him. One of his men, Brother Earl (James McDaniel), wants to position guards around the stage and podium and wants everyone attending to be searched to insure Malcolm's safety. Malcolm refuses, saying he wants the attendees of the speech to feel relaxed. Malcolm also becomes angry when his staff inform him that the OAAU program hasn't been completed and that the reverend scheduled to speak before Malcolm cannot attend. The rest of the staff are excused and Malcolm speaks alone to Brother Earl, muttering about the present day being "a time for martyrs." He also refuses to postpone the engagement when Earl suggests it. Earl leaves and Malcolm prepares his notes.
In the auditorium, Betty and Malcolm's daughters are seated in the front row while Brother Benjamin 2X speaks ahead of Malcolm and introduces him. Malcolm steps to the podium and greets the crowd when a man in the back row suddenly starts shouting at someone... intended as a distraction. While the security guards run over and deals with the yelling man (exactly as planned), a man in the second row runs up to the stage and opens fire. Malcolm smiles slightly and is hit in his left shoulder and chest by two shotgun blasts and falls to the stage. Two additional assassins in the front row also rush the stage and shoot Malcolm several more times with pistols. As the killers run out of the auditorium, one of them is caught and beaten by the angry crowd. The police arrive a few minutes later to find Betty holding her dead husband and crying. Malcolm's body is taken to a nearby hospital just down the street where he is declared dead-on-arrival from multiple gunshot wounds.
The story ends with the same eulogy delivered by Ossie Davis at Malcolm's memorial services over a montage of film and photographs of the real Malcolm. Footage of Nelson Mandela (recently released from prison after 30 years) speaking to a South African grade school class is also shown. The final shot is of Malcolm himself shouting "By any means necessary."