During his life, Malcolm went from being a drug dealer and burglar to one of the most prominent black nationalist leaders in the United States; he was considered by some as a martyr of Islam and a champion of equality. As a militant leader, Malcolm X advocated black pride, economic self-reliance, and identity politics. He ultimately rose to become a world-renowned African American/Pan-Africanist and human rights activist.

Following a pilgrimage to Mecca in 1964, Malcolm became a Sunni Muslim. Less than a year later he was assassinated in Washington Heights on the first day of National Brotherhood Week. Three members of the Nation of Islam were convicted of his assassination (one of whom confessed).

Malcolm Little was born in Omaha to Earl Little and Louise Little (née Norton). He lived briefly as an infant at 3448 Pinkney Street in the North Omaha neighborhood. His father was an outspoken Baptist lay preacher and supporter of Marcus Garvey, as well as a member of the Universal Negro Improvement Association. Malcolm described his father as a big black man who had lost one eye. According to Malcolm, three of Earl Little's brothers died violently at the hands of white men, and one of his uncles had been lynched. It is also thought that Malcolm Little's family was affiliated with the Seventh-day Adventist Church. In the autobiography, there are several references to associations with Seventh-day Adventists in Michigan and many of his lieutenants in the Nation of Islam were converts from the Seventh-day Adventist Church.

Earl Little had three children (Ella, Mary, and Earl, Jr.) by a previous marriage before he married Malcolm's mother. From his second marriage he had eight children, of whom Malcolm was the fourth. (Earl and Louise Little's children's names were, in order, Wilfred, Hilda, Philbert, Malcolm, Reginald, Wesley, Yvonne, and Robert.)

Louise Little was born in Grenada and, according to Malcolm, she looked more like a white woman. Her father was a white man of whom Malcolm knew nothing except what he described as his mother's shame. Malcolm got his light complexion from him. Initially he felt it was a status symbol to be light-skinned but later he would say that he “hated every drop of that white rapist's blood that is in me.” As Malcolm was the lightest child in the family, he felt that his father favored him; however, his mother gave him more hell for the same reason. One of his nicknames, "Red," derived from the reddish tinge of his hair. He was described as having, at birth, "ash-blonde hair ... tinged with cinnamon," and at four, "reddish-blonde hair." His hair darkened as he aged, but resembled the hair of his paternal grandmother whose hair "turned reddish in the summer sun."

According to The Autobiography of Malcolm X, his mother had been threatened by Ku Klux Klansmen while she was pregnant with him in December of 1924; his mother recalled that the family was warned to leave Omaha, because his father's involvement with UNIA was, according to the Klansmen, "stirring up trouble".

After Malcolm was born, the family relocated to Milwaukee, Wisconsin in 1926, and then to Lansing, Michigan shortly thereafter. In 1931, his father was found dead having been run over by a streetcar in Lansing. Authorities ruled his death suicide . Malcolm claimed that this cause of death was disputed by the Black community at the time, and he later disputed it himself, saying that his family had frequently found themselves the target of harassment by the white-supremacist Black Legion, which group his father accused of burning down their home in 1929. Malcolm wondered how his father could bash himself in the head and then lay down across street tracks to get run over.

Though Malcolm’s father had two life insurance policies, his mother received death benefits solely from the smaller policy. Malcolm claimed that insurance company that had issued the larger policy claimed that Earl Little's death had been a suicide, and accordingly refused to pay. Louise Little succumbed to a mental breakdown and was declared legally insane in December 1938. Malcolm and his siblings were split up and sent to different foster homes. Louise Little was formally committed to the State Mental Hospital at Kalamazoo, Michigan, and remained there until Malcolm and his brothers and sisters had her released twenty-six years later.

The Autobiography of Malcolm X states that, following the death of his father, Malcolm Little lived on Charles Street in downtown East Lansing. However, the 1930 U.S. Census (released in 2002) shows him living on a completely different Charles Street, in the low-income Urbandale neighborhood in Lansing Township, between Lansing and East Lansing. Later, at the time he was in high school, he lived in Mason, an almost all-white small town twelve miles to the south.

Malcolm X graduated from junior high school at the top of his class, but dropped out soon after an admired teacher told him that his aspirations of being a lawyer were "no realistic goal for a nigger". After enduring a series of foster homes, Malcolm was first sent to a detention center and then later moved to Boston to live with his older half-sister, Ella Little Collins.

Malcolm found work as a shoe-shiner at a Lindy Hop nightclub; in The Autobiography of Malcolm X, he says that he once shined the shoes of Duke Ellington and other notable African-American musicians. He was also employed for a time by New Haven Railroad, a job he would retain when he relocated to New York City in 1943. After some time, in Harlem, known as "Detroit Red" he became involved in drug dealing, gambling, racketeering, and robbery (all of which Malcolm collectively referred to as "hustling").

When Malcolm was examined for the World War II draft, military physicians classified him to be "mentally disqualified for military service." He explains in his autobiography that he put on a display to avoid the draft by telling the examining officer that he couldn't wait to organize with other Black soldiers and get his hands on a gun so he could "kill some crackers". His approach worked, and he was given a classification that ensured he would not be drafted.

In early 1946, he was arrested for a burglary after trying to sell stolen goods to a pawnshop. This burglary he had committed together with another African-American man and two white women, a fact which was considered particularly sensitive. The women blamed the two African-American youths for forcing them into the crime. Malcolm received a sentence of ten years in prison. While incarcerated, Malcolm, encouraged by an older fellow inmate who recognized his talent, started to read voraciously and developed astigmatism. During this time, he received correspondence from his brother Reginald telling him about the Nation of Islam, to which Malcolm subsequently converted. He was in regular contact with Elijah Muhammad during his incarceration; upon being paroled, he would go to work for the Nation of Islam. Little also belonged to a prison debating team that competed against teams from Harvard and MIT. According to the Autobiography, Malcolm started to gain fame among prisoners, but also remained under the keen eye of the authorities, who recognized in him a force that could potentially foment trouble, and who did not grant him the expected early release after five years because they believed he was too dangerous to be released early.

On March 20, 1964, Life published a famous photograph of Malcolm X holding an M1 Carbine and pulling back the curtains to peer out of a window. The photo was taken in connection with Malcolm's declaration that he would defend himself from the daily death threats which he and his family were receiving. Undercover FBI informants warned officials that Malcolm X had been marked for assassination.

Tensions increased between Malcolm and the Nation of Islam. It was alleged that orders were given by leaders of the Nation of Islam to "destroy" Malcolm; in The Autobiography of Malcolm X, he says that as early as 1963, a member of the Seventh Temple confessed to him having received orders from the Nation of Islam to kill him. The NOI sued to reclaim Malcolm's home in Queens, which they claimed to have paid for, and won. He appealed, and was angry at the thought that his family might soon have no place to live. Then, on February 14, 1965, the night before the property was to have been turned over the NOI, the house burned to the ground. Malcolm and his family survived, and no one was charged with any crime.

A week later on February 21 in Manhattan's Audubon Ballroom, Malcolm had just begun delivering a speech when a disturbance broke out in the crowd of 400. A man yelled, "Get your hand outta my pocket! Don't be messin' with my pockets!" As Malcolm's bodyguards moved to quiet the disturbance and Malcolm appealed for peace, a man rushed forward and shot Malcolm in the chest with a sawed-off shotgun. Two other men charged the stage and fired handguns at Malcolm, who was shot 16 times. Angry onlookers in the crowd caught and beat the assassins as they attempted to flee the ballroom. The 39-year-old Malcolm was pronounced dead on arrival at New York's Columbia Presbyterian Hospital. He was killed by the shotgun blast, the other bullets having been directed to his legs.

Although a police report once existed stating that two men were detained in connection with the shooting, that report disappeared, and the investigation was inconclusive. Two suspects were named by witnesses — Norman 3X Butler (Muhammad Abd Al-Azi) and Thomas 15X Johnson (Khalil Islam).

Three men were eventually charged in the case. Talmadge Hayer confessed to having fired shots into Malcolm's body, but he testified that Butler and Johnson were not present and were not involved in the shooting. All three were convicted.

Fifteen hundred people attended Malcolm's funeral in Harlem on February 27, 1965 at the Faith Temple Church of God in Christ (now Child's Memorial Temple Church of God in Christ). Ossie Davis, alongside Ahmed Osman, delivered a eulogy, describing Malcolm as "Our shining black prince". Malcolm X was buried at the Ferncliff Cemetery in Hartsdale, New York. At the gravesite after the ceremony, friends took the shovels away from the waiting gravediggers and buried Malcolm themselves. Later that month, actress Ruby Dee and Sidney Poitier became co-chairs of the New York affiliate of the Educational Fund for the Children of Malcolm X Shabazz. Civil rights leader and surgeon, T.R.M. Howard, was the chair of the Chicago affiliate of the Fund.