Background Plasmodium falciparum malaria is a threat to public health, but Plasmodium vivax malaria is most prevalent in Latin America, where the incidence rate has been increasing since 2016, particularly in Venezuela and Brazil. The Brazilian Amazon reported 193,000 cases in 2017, which were mostly confirmed as P. vivax (~ 90%). Herein, the relationships among malaria incidence rates and the proportion of accumulated deforestation were contrasted using data from the states of Acre and Rondônia in the south-western Brazilian Amazon. The main purpose is to test the hypothesis that the observed difference in incidence rates is associated with the proportion of accumulated deforestation. Methods An ecological study using spatial and temporal models for mapping and modelling malaria risk was performed. The municipalities of Acre and Rondônia were the spatial units of analysis, whereas month and year were the temporal units. The number of reported malaria cases from 2009 until 2015 were used to calculate the incidence rate per 1000 people at risk. Accumulated deforestation was calculated using publicly available satellite images. Geographically weighted regression was applied to provide a local model of the spatial heterogeneity of incidence rates. Time-series dynamic regression was applied to test the correlation of incidence rates and accumulated deforestation, adjusted by climate and socioeconomic factors. Results The malaria incidence rate declined in Rondônia but remained stable in Acre. There was a high and positive correlation between the decline in malaria and higher proportions of accumulated deforestation in Rondônia. Geographically weighted regression showed a complex relationship. As deforestation increased, malaria incidence also increased in Acre, while as deforestation increased, malaria incidence decreased in Rondônia. Time-series dynamic regression showed a positive association between malaria incidence and precipitation and accumulated deforestation, whereas the association was negative with the human development index in the westernmost areas of Acre. Conclusion Landscape modification caused by accumulated deforestation is an important driver of malaria incidence in the Brazilian Amazon. However, this relationship is not linearly correlated because it depends on the overall proportion of the land covered by forest. For regions that are partially degraded, forest cover becomes a less representative component in the landscape, causing the abovementioned non-linear relationship. In such a scenario, accumulated deforestation can lead to a decline in malaria incidence.