The idea for a medical garden was the brainchild of Susan Carlton Smith (later Cavanagh) who was a local nature artist. She proposed the idea to G.S.T. Cavanagh, the director of the Duke Medical Center Library and curator of the history of medicine collections. In 1968, a letter from Cavanagh was sent to the Hospital Auxiliary requesting funds for a potential garden. The Garden was created in 1977.
An initial guide to the Garden was produced by Smith and Cavanagh in 1978. In 2002, Christine Davis, a graduate botany student, revised the guide with expanded entries, scholarly citations, and additional indexes.