Background: Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar’s diverse ecosystems experiencing rapid ecological change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset.Methods: Here, we assess (1) the ecological correlates of malaria vector breeding through larval surveys, and (2) the socioeconomic, demographic, and ecological risk factors for malaria infection in four ecological regions of rural Madagascar. We determine risk factors using multilevel models for each unique ecological region of included in the study.Results: We find that regardless of the region, the presence of forms of aquatic agriculture around a community are predictive of the presence of malaria vectors. We determine that ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity.Conclusions: Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.