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Malaria, Chagas disease, and cutaneous leishmaniasis are endemic in the Amazon. Changes in landscape caused by deforestation and fragmentation can support transmission of malarial parasites through the increased dominance of anopheline vectors that augments human exposure to infectious bites. As for Chagas disease and cutaneous leishmaniasis, accumulated knowledge on this respect is still scant. Here the relationships between each of these diseases and changes in the landscape structure of 773 municipalities in the Brazilian Amazon were assessed from 2007 to 2019. Disease specific responses to forest cover loss and fragmentation were observed. As expected, deforestation and fragmentation of preserved municipal landscapes were drivers of the highest number of malaria cases. Deforestation, but not fragmentation, was determinant of increased numbers of cases of cutaneous leishmaniasis in preserved (≥ 50% forest cover) municipal landscapes. Municipalities with remaining forests contiguous to deforested areas modified into crops of Açai trees represent the microcosm of Chagas disease in the Amazon. Interpretations from these results allowed us to distil a general pattern. The loss of biodiversity in preserved landscapes can increase the risk of vector-borne disease in the Amazon up to a given threshold (50% of forest cover). Below this level, the risks might be lower, but there will be no biodiversity left to be preserved in the degraded landscape (< 50% forest cover). One further idea can be logically deducted from this general pattern. The concept of ‘healthy landscapes’ depends on the disease under study. In this respect, malaria and cutaneous leishmaniasis can both be prevented if deforestation and fragmentation of preserved landscapes are controlled. This leads to the concept of multifunctional landscapes, where landscape-based interventions have multiple functions, including precluding cases of two or more diseases. A multifunctional landscape approach will help in the landscape management and restoration to prevent endemic diseases and future pandemics.