Born in Taplow, Buckinghamshire, his mother was a Scottish-Irish teacher. His father was a prosperous Swiss who migrated to Edmonton, Alberta. Brion Gysin was born in Taplow House, but after nine months his mother took him to New York to stay with one of her sisters. They then went to Kansas to stay with another.

He finished his high school at the age on 15 in Edmonton, Alberta. He then studied for two years (1932-1934) at the public school Downside College in England, and while there he started to write poetry. In 1934 he escaped to a less rigid environment at the Sorbonne in Paris, France.

He acquired his practical training in the studios, salons, and cafés of pre-war Paris. He met Max Ernst, Valentine Hugo, Salvador Dali, Gala Dali, Dora Maar, and Pablo Picasso. He also visited Gertrude Stein and Alice B Toklas. He was also introduced to Paul Bowles and Jane Bowles by Denham Fouts.

In 1935, at the age of 19, he was invited to participate in the surrealist exhibition that included Arp, Duchamp, Magrite, Miró, Man Ray, and others. Unfortunately his relationship with the group broke down and André Breton ordered his work to be removed from the Galerie Aux Quatre Chemins on the eve of the opening. Brion Gysin showed his pictures on the pavement outside instead. In 1938 he travelled to Greece and made his first visit to the Algerian Sahara.

In 1939, at the age of 23, he had his first one-man show at Galerie Quatre Chemins, a Paris gallery just off the Champs Elysees. In May 1939, with the start of World War II, he was in Switzerland and made his way to New York. He worked on seven big Broadway musicals as assistant to Irene Sharaff. He gave that up and became a welder in Bayonne, New Jersey shipyards. While there he made welded sculptures. In 1943 he was then drafted into the army where he studied Japanese.

He was keenly interested in black culture and wrote a biography of the slave preacher Josiah Henson, who was a prototype for Harriet Beecher Stowe's "Uncle Tom". He also wrote The History of Slavery in Canada which he published with the help of a wealthy admirer. He was then given a Fulbright fellowship to continue his research, and in 1949-1950 he travelled around France and Spain and studied documents in the University of Bordeaux and the Archivos de India in Seville.

In the winter of 1950, when he was at a loose end in Paris, he bumped into Paul and Jane Bowles again. Paul Bowles urged him to visit them in Tangier which he did in the summer of 1951 and stayed with Paul Bowles. Paul Bowles had met Mohamed Hamri (1936-2003), a 15-year-old Arab boy native of Jajouka, a small village in the foothills of the Rif Mountains of northern Morocco, who later became an affirmed painter, and introduced him to Brion Gysin and they formed a relationship. Later, Brion Gysin moved into his own cottage.

In the winter of 1952/3 Brion Gysin mounted an exhibition, Carnet de Voyage au Sahara, in the gallery of the Hotel Rembrandt on the Boulevard Pasteur in Tangier. He was showing small pictures of the Sahara that he had made during the winter of 1951/2. It was at the exhibition in January 1953 where he first met William Burroughs but did not find him agreeable.

In 1954 Brion Gysin created 1001 Nights, a Moroccan restaurant in a narrow wing of the Menebhi palace on the Marshan. Hamri took up the job of cook. Brion Gysin employed the Master Musicians of Jajouka through whom he encountered "the magic and mystery of the Moors". In January 1958 Brion Gysin left Tangier after he had been fired by Mary Cooke, a major backer of 1001 Nights.

He went to London and then Paris where he bumped into William Burroughs on the Place St. Michel and they began an intimate friendship. They stayed in an unnamed hotel at 9 rue Git-le-Coeur that Allen Ginsberg had discovered in the mid-1950s and had come to be called The Beat Hotel. Many figures from the world of art and literature passed through at its height from about 1958 to 1963. Brion Gysin stayed in room 25.

In the summer of 1959 Brion Gysin proposed his Cut-Up method of writing where pages of text were cut up and re-arranged haphazardly. He and William Burroughs used this method to produce Minutes To Go and The Exterminator, both published in 1960. Text was taken from newspapers, letters, the Bible, the Koran, Naked Lunch, or any other text.

Brion Gysin used projections to produced light shows, and he worked with the mathematician Ian Sommerville to make Dreamachine which had light flashes complementing the alpha rhythms of the brain. It was first shown in 1962 in Paris. In 1965 Brion Gysin returned to Tangier with his new lover, the poet John Giorno, who had been part of Andy Warhol's set. Brion Gysin started work on The Process.

In 1968 Rolling Stones guitarist Brian Jones, recording engineer George Chkiantz, and a model named Suki Potier, visited Brion Gysin in Tangier . They wanted to record the ceremony of Bou Jeloud in the Moroccan mountain village of Jajouka. Unfortunately they had arrived at the wrong time of year for the ceremony, but Brion Gysin took them to the Rif mountains and Jajouka. They made tapes which were released on Rolling Stones records two years after Brian Jones's death, but with added psychedelic effects, as The Pipes Of Pan At Joujouka. The tapes were re-released in their original form by Philip Glass's Point Music label in July 1995. The soundtrack to David Cronenberg's Naked Lunch featured Jajouka music, as did Continental Drift on the Rolling Stones 1989 album, Steel Wheels.

Brion Gysin left Tangier for good and took an apartment near the Beaubourg in Paris. He became stricken with cancer and died there in 1986. A memorial gathering was held in Tangier and his ashes were thrown into the sea near the Caves of Hercules.