William S. Burroughs was born in 1914 in St. Louis, Missouri. He attended private schools in St. Louis before a brief stint at the Los Alamos Ranch School in New Mexico. He received a bachelor's degree from Harvard in 1936.

After graduating from Harvard, Burroughs spent a few years traveling through Europe, followed by a short stint in the US Army. After his discharge from the Army Burroughs moved to Chicago where he worked a string of odd jobs and spent time with his friend David Kammerer and Kammerer's obsession, University of Chicago student Lucien Carr. When Carr transferred from UC to Columbia University, both of the older men used this as an impetus to move to New York City as well.

It was through Carr that Burroughs met Allen Ginsberg and Jack Kerouac. The three, along with Carr, Kerouac's girlfriend Edie Parker and her roommate Joan Vollmer, forged close friendships centered around a shared love of literature, drugs, and a bohemian lifestyle. It was during this time that Burroughs was first introduced to narcotics through the well known Times Square hustler, and writer, Herbert Huncke and quickly became addicted to opiates. Jean Vollmer, Burroughs's lover, and later common-law wife, also suffered from an addiction that eventually resulted in her hospitalization for acute amphetamine psychosis. The two had a son, William S. Burroughs Jr., before Burroughs accidentally, but fatally, shot Vollmer in Mexico City.

Burroughs began working on the manuscript that would eventually become Junky in Mexico City before Vollmer's death. Though he had briefly worked on the short story "And the Hippos Were Boiled in Their Tanks" with Jack Kerouac, he did not have literary aspirations. Even while working on Junkie he assumed that the autobiographical novel would be an anomaly, not the beginning of a literary career.

After his trial over Vollmer's death, Burroughs thought it prudent to leave Mexico. He spent more time traveling in South America researching the hallucinatory drug yage and corresponding with Allen Ginsberg, who was by this point acting as his literary agent, about his search for the drug and its effects. These letters formed the basis of Burroughs and Ginsberg's book The Yage Letters. After the yage quest, Burroughs returned, briefly, to New York where he initiated an intense but mostly one-sided romantic and sexual relationship with Ginsberg before leaving the United States for a brief stay in Rome and then Tangier.

While in Tangier Burroughs completed the text that would become The Naked Lunch. Interzone, as he called the working manuscript, was, in opposition to his earlier works Junkie and Queer, a non-linear collection of loosely connected episodes. Allen Ginsberg, who, along with Peter Orlovsky and Jack Kerouac, had traveled to Tangier to help collect and type a clean copy of the manuscript, presented The Naked Lunch to Maurice Girodias of the Olympia Press. Though Girodias was not initially interested in the work, he did decide to print it after all in 1959. An American edition, based on a 1958 manuscript of the novel (currently part of the Allen Ginsberg Papers held by the RBML) was published by Grove Press in 1962.

Burroughs then moved to Paris where he continued writing and producing the episodic sketches that, combined with material from The Naked Lunch manuscripts, comprise The Soft Machine, The Ticket that Exploded, and Nova Express. While in Paris living in a guesthouse christened the Beat Hotel with Ginsberg, Orlovsky, Gergory Corso, and Harold Chapman, Burroughs first came into contact with Brion Gysin. Gysin, a painter, had a profound impact on Burroughs and Gysin's "cut-up technique" where strips of two different texts were aligned to create a new, composite text became a prominent feature of Burroughs's future writing.

In 1974 Burroughs returned to the United States. He accepted a teaching post at City College of New York that Allen Ginsberg had recommended him for and settled into an apartment nicknamed The Bunker on Manhattan's Lower East Side. During this time Burroughs became acquainted with James Grauerholz, a young beat devotee who became Burroughs's devoted manager, secretary, and companion.

Burroughs moved to Lawrence Kansas in 1981 and remained there until his death in 1997. During the later part of his life he wrote less and less, focusing on visual art and spoken word performances. He also appears in the Gus Van Sant movie Naked Cowboy.