Malaria remains one of the most common vector-borne diseases in the world and the definition of novel control strategies can benefit from the modeling of transmission processes. However, data-driven models are often difficult to build, as data are very often incomplete, heterogeneous in nature and in quality, and/or biased. In this context, a knowledge-based approach is proposed to build a robust and general landscape-based hazard index for malaria transmission that is tailored to the Amazonian region. A partial knowledge-based model of the risk of malaria transmission in the Amazonian region, based on landscape features and extracted from a systematic literature review, was used. Spatialization of the model was obtained by generating land use and land cover maps of the cross-border area between French Guiana and Brazil, followed by computing and combining landscape metrics to build a set of normalized landscape-based hazard indices. An empirical selection of the best index was performed by comparing the indices in terms of adequacy with the knowledge-based model, intelligibility and correlation with P. falciparum incidence rates. The selected index is easy to interpret and successfully represents the current knowledge about the role played by landscape patterns in malaria transmission within the study area. It was significantly associated with P. falciparum incidence rates, using the Pearson and Spearman correlation coefficients (up to 0.79 and 0.75, respectively; p-value