Byron de la Beckwith was born to Byron de la and Susie Southworth (Yerger) Beckwith in Colusa, California on November 9, 1920. Although his father had been a prosperous irrigation entrepreneur when he died on August 10, 1926, he left his young family deeply in debt. His widow liquidated his estate to fulfill his financial obligations (including one to his Oakland mistress, Ladye E. Cartmell) and moved herself and her young son to her hometown of Greenwood, Mississippi to live with her family. Although the Yergers had been impoverished by the Civil War, they managed to retain their home, a minimal number of black servants, and much of their social standing. There had been no Black people in Beckwith's native Colusa, but he quickly became accustomed to Greenwood's deeply entrenched racial hierarchy.

Always in fragile emotional and physical health, Susie (Yerger) Beckwith died in the early 1930s and her nephew, Yerger Morehead, was selected as her son's guardian. Beckwith was also deeply influenced by his eccentric uncle William Yerger (known as Uncle Will), who was a constant presence in his young life. After a lackluster career in Greenwood's public schools, Beckwith was sent to the strict Webb School in Bell Buckle, Tennessee in 1936. The regime proved too difficult, however, and his Uncle Will arranged for him to transfer to the Columbia Military Academy in Columbia, Tennessee in 1938. Beckwith did not succeed at Columbia either, and graduated from the Greenwood public schools in 1940. He enrolled in the University of Alabama, but transferred to Mississippi State College when he was not accepted into his first choice of fraternities. His grades were, however, so low that he soon returned to Greenwood in disgrace. Beckwith took a job marketing soft drinks throughout the Delta before enlisting in Company A of the Second Division of the U. S. Marine Corps in 1942.

During the War, Beckwith's unit was deployed to the Pacific and fought at Guadalcanal, Tulagi, and Tarawa (which was, in numerical terms, one of the costliest battles the Marines ever waged). He was later stationed at the Naval Air Station in Memphis, Tennessee, where he worked as an aviation mechanic. Here, he met Mary Louise Willie Williams, who he married on September 22, 1945. Their only son, Byron de la Beckwith Jr., was born on September 9, 1946. Beckwith's relationship with his wife was at best tempestuous. Although both took care to maintain the appearance of a typical southern family, drunken arguments were frequent and Beckwith physically and emotionally abused Willie. They were divorced and remarried twice in the early 1960s before divorcing permanently in September of 1965.

From his early years in Mississippi, Beckwith believed that his lineage entitled him to a privileged position in society. He felt himself superior to all his neighbors. He considered NAACP leader Medgar Evers to be a dangerous troublemaker intent upon destroying society's proper order. Just after midnight on June 12, 1963 Beckwith shot and killed Evers from the cover of a honeysuckle bush across the road from his Jackson, Mississippi home. Among southerners disoriented and frightened by the sudden and dramatic changes in the racial status quo, Beckwith was hailed as a hero. He was arrested for the crime on July 2, 1963, but the all-white jury hung and released Beckwith. His second trial began on April 6, 1964 but also ended without a verdict. After his second release, Beckwith returned to his work as a traveling salesman and made an unsuccessful run for Lieutenant Governor of Mississippi in 1967.

Beckwith's racism became increasingly radical as he aged. He involved himself with the Ku Klux Klan beginning in the late 1960s and was ordained a minister in the Christian Identity Movement in 1977. Beckwith was arrested again in 1973, this time on charges of plotting to assassinate A. I. Botnick, Regional Director of the Anti-Defamation League, by blowing up his home. He was acquitted of the federal charges brought against him but was sentenced to five years imprisonment at the Louisiana State Penitentiary in Angola by the state courts. He began serving his sentence in 1977 and was released in 1980 due to his good behavior. His fanaticism had not abated, however, and he continued to operate in white supremacist circles. He also married retired nurse and fellow white supremacist Thelma Lindsay Neff on June 8, 1983. The couple lived in Signal Mountain, Tennessee until Beckwith was extradited to Mississippi to once again stand trial for the murder of Medgar Evers. He was finally convicted in 1994 and died while serving his prison sentence on January 21, 2001.