Wildfires are expected to increase in the near future, mainly because of climate changes and land use management. One of the most vulnerable areas in the world is the forest in central-South America, including Bolivia. Despite that this country is highly prone to wildfires, literature is rather limited here. To fill this gap, we implemented a dataset including the burned area that occurred in the department of Santa Cruz in the period of 2010–2019, and the digital spatial data describing the predisposing factors (i.e., topography, land cover, ecoregions). The main goal was to develop a model, based on Random Forest, in which probabilistic outputs allowed to elaborate wildfires susceptibility maps. The overall accuracy was finally estimated by using 5-fold cross-validation. In addition, the last three years of observations acted as the testing dataset, allowing to evaluate the predictive performance of the model. The quantitative assessment of the variables revealed that “flooded savanna” and “shrub or herbaceous cover, flooded, fresh/saline/brakish water” are respectively the ecoregions and land cover classes with the highest probability of predicting wildfires. This study contributes to the development and validation of an innovative mapping tool for fire risk assessment, implementable at a regional scale in different areas of the globe.