Rot Before Microbes is a study of fermentation and rot before they were codified by nineteenth century microbiology. My dissertation situates fermentation and rot in the early modern Atlantic World in order to examine how various social groups interacted with and described these omnipresent biochemical processes at a time when the study, transport, and commodification of the natural world was coterminous with settler colonialism. In the early modern Atlantic World, rot and fermentation were intriguing characteristics of Native American food making; troubling dynamics decaying transatlantic seaships and natural history specimens; lucrative processes involved in the production of plantation commodities like sugar, cacao, and indigo; economic terms that marred commodities as commodity value was methodized; and odorous qualities empowering Black practitioners in doctoring, Obeah, and other ritual practices. In five case studies, my dissertation hypothesizes that diverse European colonial machinations required the control and commodification of fermentation and rot. Moreover, employing the methodologies of post-colonial historians of science, my dissertation foregrounds fermentation and rot as two under-examined sites of early modern knowledge making, especially the knowledge making of those social groups who have generally been left out of the history of science.