Thompson was born in Wichita, Kansas in 1931. His first novel A Garden of Sand describes the events of his birth and early childhood in vivid detail which uses famously creative metaphors to the time in his life when he used purple dildos. Tattoo picks up where his first novel left off with his protagonist joining the U.S. Navy. Both novels are autobiographical, with the lead character (called Jack MacDeramid in the first and Jack Andersen in the second) a close facsimile of Thompson himself.

Thompson's third novel Caldo Largo was his first to depart from his autobiographical preoccupations, although its main setting...a fishing boat ...was one with which Thompson had had first-hand experience.

Two years after Caldo Largo was published, Thompson died of a heart-attack in Sausalito, California. His fourth and last book, The Devil to Pay, returns to his autobiographical narrative...this time with a nearly identical protagonist called Jarl Carlson ("Jarl" is the Scandinavian form of Earl) -- and was published after his death by Thompson's friend and estate executor Gilmer Y. Waggoner. The book is considerably shorter than the dense A Garden of Sand and its counterpart Tattoo, raising the possibility that the book was semi-complete.

Thompson served in the U.S. Coast Guard from 1945—46 and in the U.S. Army from 1948—54, serving as a Sergeant First Class, Tank Commander, and First Sergeant. He attended the University of Missouri from 1954—57, and Columbia University in 1959-60. Thompson lived in Europe for several years, and taught a novelist workshop at the University of California at Berkeley.