Cannabis and tobacco have longstanding roles in African societies. Despite botanical and pharmacological dissimilarities, it is worthwhile to consider tobacco and cannabis together because they have been for centuries the most commonly and widely smoked drug plants. Cannabis, the source of marijuana and hashish, was introduced to eastern Africa from southern Asia, and dispersed widely within Africa mostly after 1500. In sub-Saharan Africa, cannabis was taken into ethnobotanies that included pipe smoking, a practice invented in Africa; in Asia, it had been consumed orally. Smoking significantly changes the drug pharmacologically, and the African innovation of smoking cannabis initiated the now-global practice. Africans developed diverse cultures of cannabis use, including Central African practices that circulated widely in the Atlantic world via slave trading. Tobacco was introduced to Africa from the Americas in the late 1500s. It gained rapid, widespread popularity, and Africans developed distinctive modes of tobacco production and use. Primary sources on these plants are predominantly from European observers, which limits historical knowledge because Europeans strongly favored tobacco and were mostly ignorant or disdainful of African cannabis uses. Both plants have for centuries been important subsistence crops. Tobacco was traded across the continent beginning in the 1600s; cannabis was less valuable but widely exchanged by the same century, and probably earlier. Both plants became cash crops under colonial regimes. Tobacco helped sustain mercantilist and slave-trade economies, became a focus of colonial and postcolonial economic development efforts, and remains economically important. Cannabis was outlawed across most of the continent by 1920. Africans resisted its prohibition, and cannabis production remains economically significant despite its continued illegality.