Southeastern Brazil has seen dramatic landscape modifications in recent decades, due to expansion of agriculture and urban areas; these changes have influenced the distribution and abundance of vertebrates. We developed predictive models of ecological and spatial distributions of capybaras (Hydrochoerus hydrochaeris) using ecological niche modeling. Most occurrences of capybaras were in flat areas with water bodies surrounded by sugarcane and pasture. More than 75% of the Piracicaba River basin was estimated as potentially habitable by capybara. The models had low omission error (2.3–3.4%), but higher commission error (91.0–98.5%); these “model failures” seem to be more related to local habitat characteristics than to spatial ones. The potential distribution of capybaras in the basin is associated with anthropogenic habitats, particularly with intensive land use for agriculture.