We investigate the ecological and evolutionary variables that best explain spatial diversity patterns of anuran amphibians in three of South America’s most diverse and geographically widespread domains: the Cerrado, Amazonia, and Atlantic Rainforest. We used Conditional Autoregressive Models to assess the potential influence of present-day climate (temperature and precipitation), historical climate (stability over the last 120,000 years), potential evapotranspiration (PET), and topography (slope, aspect, and rugosity) on spatial variation in taxonomic, functional, and phylogenetic diversity at a resolution of 0.5 x 0.5 degrees. Both taxonomic diversity and phylogenetic diversity increased with long-term climatic stability in all regions. By contrast, functional diversity was negatively impacted by precipitation of the driest quarter. However, the relative importance of each predictor variable differed among diversity dimensions and domains. In the Atlantic Rainforest, potential evapotranspiration was positively correlated with functional diversity, but negatively associated with taxonomic and phylogenetic diversity. In Amazonia, precipitation and relief slopes were positively associated with functional and phylogenetic diversity, respectively, while relief slopes were negatively correlated with taxonomic diversity. In the Cerrado, precipitation was negatively correlated with functional diversity, but climatic stability was more strongly associated with phylogenetic and taxonomic diversity. These findings indicate that present-day climatic factors are critical in forested domains, whereas a combination of historical and current variables is more relevant in the Cerrado. Notably, ecotones exhibit significantly higher functional diversity, likely reflecting the encounter of faunas from adjacent domains having distinct ecological regimes. Characterizing the drivers of heterogeneous biodiversity distribution offers insights into the assembly of ecological communities in other tropical and transitional ecosystems and can potentially guide conservation strategies globally.