The historic port town of Mikindani is situated along the southern portion of the Swahili coast. Archaeological investigations in this region of coastal East Africa yield evidence of occupation since the last centuries BCE and intensive settlement since the middle of the first millennium CE. This long settlement history suggests that people in the region have had an expansive, wide-ranging impact on local ecological conditions in the region. This paper takes a historical ecology approach in evaluating the nature and degree of anthropogenic influences on the environment in and around Mikindani. The evaluation is based on evidence from contemporary botanical communities, faunal remains, macrobotanicals, phytolith residues, isotope analysis of archaeological sediments, and soil chemistry. This research also looks to define an environmental component that contributes to a previously defined mercantile culture that characterizes Swahili communities in the region. We argue that this interdisciplinary analysis yields evidence of several long-term anthropogenic influences in Mikindani, including: a long-term reduction in forests and woody vegetation, reliance on shifting agriculture as a subsistence strategy, and the continued reliance on marine resources to meet subsistence needs. These patterns of human-environment interaction help suggest reasons for certain developments in Mikindani’s history, perhaps most notably its early second millennium CE absence from Indian Ocean trade networks. Our results contribute to a growing literature in East Africa which acknowledges that modern environments of East Africa derive from a recursive relationship with human populations that has continued for thousands of years.