This chapter outlines current knowledge about cassava’s origin in Amazonia and summarizes the history of its introduction and diffusion in the Old World. The chapter examines the evolution of the traits that led to its success, focusing on two aspects under-appreciated by cassava breeders, extension specialists and other stakeholders: the management of a crop that is chemically defended against enemies but potentially toxic to human consumers, and the creation of a mixed clonal/sexual reproductive system that is vital for maintaining the crop’s adaptive potential. The chapter shows that these features arose through the biocultural coevolution of the plant’s traits and farmer practices in Amazonia, and argues that imperfect transmission of cultural practices associated with cassava cultivation led initially to maladaptive mismatches that necessitated the partial re-invention of cassava cultivation in the crop’s diasporic populations.