Mechoulam was born in Sofia, Bulgaria in 1930,He gained his first research experience in the Israeli Army working on insecticides.He received his M.Sc. in biochemistry from the Hebrew University of Jerusalem (1952), and his Ph.D. at the Weizmann Institute, Reḥovot (1958), with a thesis on the chemistry of steroids. After postdoctoral studies at the Rockefeller Institute, New York (1959–60), he was on the scientific staff of the Weizmann Institute (1960–65), before moving to the Hebrew University of Jerusalem, where he became professor (1972) and Lionel Jacobson Professor of Medicinal Chemistry from 1975. He was rector (1979–82) and pro-rector (1983–85). In 1994 he was elected a member of the Israel Academy of Sciences. Mechoulam is one of the founding members of the International Association for Cannabinoid Medicines.