The book is structured as a series of loosely connected vignettes. Burroughs stated that the chapters are intended to be read in any order. The reader follows the narration of junkie William Lee, who takes on various aliases, from the U.S. to Mexico, eventually to Tangier and the dreamlike Interzone.

The vignettes are drawn from Burroughs' own experiences in these places and his addiction to drugs (heroin, morphine, and while in Tangier, majoun [a strong hashish confection] as well as a German opioid, brand name Eukodol, of which he wrote frequently).

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