Visceral leishmaniasis (VL) is an urgent public health concern in Brazil. We evaluated the spatiotemporal distribution of VL to better understand the effects of economic activities related to agriculture, livestock, and deforestation on its incidence in the Brazilian Legal Amazon (BLA). The data on newly confirmed cases of VL in Brazilian municipalities from 2007 to 2020 were extracted from the Brazilian Notifiable Diseases Information System (SINAN) and analyzed. The data on agricultural production (planted area in hectares) and livestock (total number of cattle) were obtained from the Brazilian Institute of Geography and Statistics (IBGE), whereas deforestation data (in hectares) were obtained from the Amazon Deforestation Estimation Project (PRODES). SatScan and the local indicators of spatial association (LISA) were used to identify the spatial and temporal patterns of VL and its relationships with economic and environmental variables. The cumulative incidence rate was found to be 4.5 cases per 100,000 inhabitants. Based on the LISA results, areas with a high incidence of VL and deforestation were identified in the states of Roraima, Pará, and Maranhão. Strengthening deforestation monitoring programs and environmental enforcement actions can help implement public policies to control illegal deforestation and mitigate the socio-environmental vulnerability in the BLA. Therefore, areas identified in this study should be prioritized for controlling VL.