After attending The Tokyo College of Photography in the 1950s Hosoe, joined “Demokrato” an avant-garde artist's group led by the artist Ei Q, while still a student. In 1960, Hosoe created the Jazz Film Laboratory (Jazzu Eiga Jikken-shitsu) with Hijikata, Shuji Terayama, and Shōmei Tōmatsu. The Jazz Film Laboratory was a multidisciplinary artistic project aimed at producing highly expressive and intense works such as Hosoe's 1960 short black and white film Navel and A-Bomb (Heso to genbaku).

With Hijikata, Hosoe created Kamaitachi, a series of images that reference stories of a supernatural being — 'weasel-sickle' — that haunted the Japanese countryside of Hosoe's childhood. In the photographs, Hijikata is seen as a wandering ghost mirroring the stark landscape and confronting farmers and children.

With Mishima as a model, Hosoe created a series of dark, erotic images centered on the male body, Ordeal by Roses (Bara-kei, 1963). The series (set in Mishima's Tokyo house) positions Mishima in melodramatic poses. Mishima would follow his fantasies, eventually committing suicide by seppuku in 1970.

Hosoe has been the director of the Kiyosato Museum of Photographic Arts (Kiyosato, Yamanashi) since its opening in 1995.