Salvia divinorum has been used for centuries by the Mazatec Indians, living in remote regions of Oaxaca where it first came to the awareness of western researchers in the first half of the 20th century. Not much is known regarding the plant's use before this time, although there is some indication that it may have been used by the Aztecs in earlier times. The first time the plant was described in western literature was by Swedish anthropologist Jean Basset Johnson in 1939. Johnson, who was investigating psilocybe mushroom use amongst the Mazatecs at the time , also noted the use of Salvia divinorum in healing and sacred ceremonies.

Salvia divinorum is a very rare plant, only being found in a few ravine areas in the Sierra Mazateca mountains. The plant is propagated with ease by making cuttings, and during the last few decades has found its way into various botanical gardens and private collections