Malaria control in South America has vastly improved in the past decade, leading to a decrease in the malaria burden. Despite the progress, large parts of the continent continue to be at risk of malaria transmission, especially in northern South America. The objectives of this study were to assess the risk of malaria transmission and vector exposure in northern South America using multi-criteria decision analysis. The risk of malaria transmission and vector exposure in northern South America was assessed using multi-criteria decision analysis, in which expert opinions were taken on the key environmental and population risk factors. Results from our risk maps indicated areas of moderate-to-high risk along rivers in the Amazon basin, along the coasts of the Guianas, the Pacific coast of Colombia and northern Colombia, in parts of Peru and Bolivia and within the Brazilian Amazon. When validated with occurrence records for malaria, An. darlingi, An. albimanus and An. nuneztovari s.l., t-test results indicated that risk scores at occurrence locations were significantly higher (p < 0.0001) than a control group of geographically random points. In this study, we produced risk maps based on expert opinion on the spatial representation of risk of potential vector exposure and malaria transmission. The findings provide information to the public health decision maker/policy makers to give additional attention to the spatial planning of effective vector control measures. Therefore, as the region tackles the challenge of malaria elimination, prioritizing areas for interventions by using spatially accurate, high-resolution (1 km or less) risk maps may guide targeted control and help reduce the disease burden in the region.