His book The Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers (1979), co-authored with chemist Albert Hofmann, the discoverer of LSD, is considered his greatest popular work: it has never been out of print and was revised into an expanded second edition, based on a German translation by Christian Rätsch (1998), in 2001.

[3] Ames became a mentor, and Schultes became an assistant in the Botanical Museum; his undergraduate senior thesis studied the ritual use of peyote cactus among the Kiowa of Oklahoma, obtaining a degree in biology in 1937.

Schultes' doctoral thesis investigated the lost identity of the Mexican hallucinogenic plants teonanácatl mushrooms belonging to the genus Psilocybe, and ololiuqui, a morning glory species, in Oaxaca, Mexico.

[3] Schultes' botanical field-work among aboriginal American communities led him to be one of the first to alert the world about destruction of the Amazon rain-forest and the disappearance of its native people.

His ever-popular undergraduate course on economic botany was noted for his Victorian demeanor, lectures delivered in a white lab coat, insistence on memorization of systematic botanical names, films depicting native ritual use of plant inebriants, blowgun demonstrations, and hands-on labs (using plant sources of grain, paper, caffeine, dyes, medicines, and tropical fruits).

In Western culture, Schultes' discoveries influenced writers who considered hallucinogens as the gateways to self-discovery, such as Aldous Huxley, William Burroughs and Carlos Castaneda.

[1][5] Although he contributed to the psychedelic era with his discoveries, he personally disdained its proponents, dismissing drug guru and fellow Harvard professor Timothy Leary for being so little versed in hallucinogenic species that he misspelled the Latin names of the plants.

"[1][4][5] Schultes' personal hero was Richard Spruce, a British naturalist who spent seventeen years exploring the Amazon rainforest.

In 1962, botanist Harold E. Moore published Resia, which is a genus of flowering plants from South America, in the family Gesneriaceae and named in his honour.