Dams have homogenized regional river flow regimes across the continental United States, reducing geographic variation in streamflow patterns and altering natural disturbance regimes that support biodiversity. This study used 186 long-term streamflow records to show that dams have homogenized flow regimes on third- through seventh-order rivers in 16 historically distinct hydrologic regions over the 20th century. Dams primarily affect the magnitude and timing of high and low flows, reducing regional differences in natural flow regimes. In contrast, undammed reference rivers showed no evidence of homogenization, despite documented changes in regional precipitation. The average density of dams is one every 48 km of river channel, suggesting a continental-scale effect of homogenizing environmental templates, which favors non-native species over locally adapted ones. Quantitative analyses support the conclusion that dams have homogenized regional flow regimes, reducing the distinctiveness of natural disturbance dynamics. This homogenization may override regional-scale differences in climate and geology that shape ecosystem resilience and biodiversity. The study highlights the need for conservation strategies to maintain regional distinctiveness in river ecosystems to support biodiversity and ecosystem function. Dams have significantly altered global water and sediment fluxes, threatening native river biodiversity. The cumulative effects of dams on river ecosystems may lead to global-scale convergence of historically distinct environmental templates, diminishing regional-scale variation that supports native biodiversity. The study emphasizes the importance of preserving intact river systems and implementing management strategies to restore natural flow regimes and maintain ecosystem resilience.Dams have homogenized regional river flow regimes across the continental United States, reducing geographic variation in streamflow patterns and altering natural disturbance regimes that support biodiversity. This study used 186 long-term streamflow records to show that dams have homogenized flow regimes on third- through seventh-order rivers in 16 historically distinct hydrologic regions over the 20th century. Dams primarily affect the magnitude and timing of high and low flows, reducing regional differences in natural flow regimes. In contrast, undammed reference rivers showed no evidence of homogenization, despite documented changes in regional precipitation. The average density of dams is one every 48 km of river channel, suggesting a continental-scale effect of homogenizing environmental templates, which favors non-native species over locally adapted ones. Quantitative analyses support the conclusion that dams have homogenized regional flow regimes, reducing the distinctiveness of natural disturbance dynamics. This homogenization may override regional-scale differences in climate and geology that shape ecosystem resilience and biodiversity. The study highlights the need for conservation strategies to maintain regional distinctiveness in river ecosystems to support biodiversity and ecosystem function. Dams have significantly altered global water and sediment fluxes, threatening native river biodiversity. The cumulative effects of dams on river ecosystems may lead to global-scale convergence of historically distinct environmental templates, diminishing regional-scale variation that supports native biodiversity. The study emphasizes the importance of preserving intact river systems and implementing management strategies to restore natural flow regimes and maintain ecosystem resilience.