Over the last few decades, the occupation of the Amazon and the expansion of large-scale economic activities have exerted a significant negative impact on the Amazonian environment and on the health of the Amazon’s inhabitants. These processes have altered the context of the manifestation of health problems in time and space and changed the characteristics of the spatial diffusion of health problems in the region. This study analyzed the relationships between the various economic processes of territorial occupation in the Amazon and the spatial diffusion of homicidal violence through the configuration of networks of production, as well as the movements of population and merchandise. Statistical data on violence, deforestation, the production of agricultural items, and socio-economic variables, georeferenced and available for the 771 municipalities of the Legal Amazon were used in this study. The results suggest that the diffusion of violence closely follows the economic expansion front, which is related to deforestation and livestock production but has little relation to grain production, demonstrating steps and typologies of recent occupation in the Amazon that promote violence. These spatial patterns reveal environmental and socio-economic macro-determinants that materialize in geographic space through the construction of highways and the formation of city networks.