The Central African Republic (CAR) has experienced repeated mpox outbreaks since 2001. Although several mpox epidemiological risk factors for zoonotic and interhuman transmis- sion have been documented, the reasons for more frequent epidemic outbreaks are less well understood, relying on vague explanatory categories, including deforestation, hunting, and civil unrest. To gain insight into increasingly frequent outbreaks, we undertook an ethno- historical, eco-anthropological analysis in two CAR regions: the Lobaye prefecture, experiencing one or more annual outbreaks in the past decade, and the Sangha-Mbaere prefecture, with a longer history of mpox but less frequent outbreaks. We comparatively examined changing political economies, forest use practices, and understandings of mpox. In 2022, we conducted 40 qualitative ethnohistorical, anthropological interviews and participant-observation of forest activities in two languages (Sango and French). We compared contemporary practices with hunting, trapping, and meet consumption practices, documented through quantitative and qualitative observation in one research site, over 6 months in 1993. We find increased rodent capture and consumption in both sites in the past 30 years and expanded practices of other potentially risky activities. Simultaneously, we also identify important differences in risky practices between our Lobaye and Sangha-Mbaere participants. In addition, Lobaye and Sangha participants underscored historical processes of decline producing mpox among other emergences, but they framed these declension processes diversely as economic, political, nutritional, and moral. Our findings are important because they mobilize new types of evidence to shed light on the processual dynamics of mpox outbreaks in the CAR. This study also reveals variability across two sites within the same country, highlighting the importance of comparative, fine-grained anthropological and historical research to identify underlying dynamics of mpox outbreaks. Finally, our study points to the need for mpox interventions and risk communication accounting for these regional differences, even within a single country.