In modern ecosystems, regions of topographic heterogeneity, when compared with nearby topographically homogeneous regions, support high species densities of mammals and other groups. This biogeographic pattern could be explained by either greater diversification rates or greater accommodation of species in topographically complex regions. In this context, we assess the hypothesis that changes in landscape history have stimulated diversification in mammals. Landscape history includes tectonic and climatic processes that influence topographic complexity at regional scales. We evaluated the influence of changes in topographic complexity and climate on origination and extinction rates of rodents, the most diverse clade of mammals. We compared the Neogene records of rodent diversity for three regions in North America. The Columbia Basin of the Pacific Northwest (Region 1) and the northern Rocky Mountains (Region 2) were tectonically active over much of the Cenozoic and are characterized by high topographic complexity today. The northern Great Plains (Region 3) have been tectonically quiescent, with low relief, throughout the Cenozoic. These three regions have distinctive geologic histories and substantial fossil records. All three regions showed significant changes in diversification and faunal composition over the Neogene. In the montane regions, originations and extinctions peaked at the onset and close, respectively, of the Miocene Climatic Optimum (17–14 Ma), with significant changes in faunal composition accompanying these episodes of diversification. In the Great Plains, rodents showed considerable turnover but infrequent diversification. Peak Neogene diversity in the Great Plains occurred during cooling after the Miocene Climatic Optimum. These histories suggest that climatic changes interacting with increasing topographic complexity intensify macroevolutionary processes. In addition, close tracking of diversity and fossil productivity with the stratigraphic record suggests either large-scale sampling biases or the mutual response of diversity and depositional processes to changes in landscape history.