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The Amazon biome is under severe threat due to increasing deforestation rates and loss of biodiversity and ecosystem services while sustaining a high burden of neglected tropical diseases. Approximately two thirds of this biome are located within Brazilian territory. There, socio-economic and environmental landscape transformations are linked to the regional agrarian economy dynamics, which has developed into six techno-productive trajectories (TTs). These TTs are the product of the historical interaction between Peasant and Farmer and Rancher practices, technologies and rationalities. This article investigates the distribution of the dominant Brazilian Amazon TTs and their association with environmental degradation and vulnerability to neglected tropical diseases. The goal is to provide a framework for the joint debate of the local economic, environmental and health dimensions. We calculated the dominant TT for each municipality in 2017. Peasant trajectories (TT1, TT2, and TT3) are dominant in ca. fifty percent of the Amazon territory, mostly concentrated in areas covered by continuous forest where malaria is an important morbidity and mortality cause. Cattle raising trajectories are associated with higher deforestation rates. Meanwhile, Farmer and Rancher economies are becoming dominant trajectories, comprising large scale cattle and grain production. These trajectories are associated with rapid biodiversity loss and a high prevalence of neglected tropical diseases, such as leishmaniasis, Aedes-borne diseases and Chagas disease. Overall, these results defy simplistic views that the dominant development trajectory for the Amazon will optimize economic, health and environmental indicators. This approach lays the groundwork for a more integrated narrative consistent with the economic history of the Brazilian Amazon.