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Although the importance of biogeography in the speciation process is well recognized, the fundamental role of geographic diversification during adaptive radiations has not been studied to determine its importance during the adaptive radiation process. We examined the relationship between lineage and regional diversification patterns in the South American rodent subfamily Sigmodontinae, one of the best candidates for an adaptive radiation in mammals, to propose a conceptual framework for geographic transitions during adaptive radiations. We reconstructed a time-calibrated phylogeny from four nuclear genes and one mitochondrial gene for 77% of sigmodontine diversity. Historical biogeography was reconstructed among 14 regions, for which we applied a sliding-window approach to estimate regional transition rates through time. We compared these rate patterns and measured whether regions consisted of species that were more phylogenetically related than expected by chance. Following the initial South American colonization around 7 million years ago, multiple expansions from northern regions correlated with a burst of speciation. Subsequently, both diversification and regional transition rates decreased overall and within the majority of regions. Despite high regional transition rates, nearly all regional assemblages were phylogenetically clustered, indicating that within-region diversification was common. We conclude that biogeographic complexity and partitioning played a profound role in the adaptive radiation of the South American Sigmodontinae (Oryzomyalia), the degree to which is determined by the relative scales of spatial variation and dispersal abilities.