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In the eastern United States, existing paleo-reconstructions in fluvial environments consist primarily of site-specific investigations of climate and human impacts on riverine processes. This paper presents the first meta-analysis of fluvial reconstructions focused on regional watersheds of the eastern United States, including the Lower Mississippi, Tennessee, South Atlantic–Gulf Coast, Ohio, Mid-Atlantic, and New England regional watersheds. Chronologies of fluvial activity (i.e. alluvial deposition) and stability (i.e. landscape stability) were developed by synthesizing data from existing, published, and site-specific fluvial reconstruction studies conducted across the eastern United States. Overall, regional watersheds show variable patterns of synchronicity across watersheds and did not demonstrate cyclic behavior through the Holocene. During the last millennium, only the Lower Mississippi and Ohio regional watersheds exhibit high rates of fluvial activity active during the 'Medieval Climate Anomaly' (650–1050 yr BP), while nearly all other regional watersheds in the eastern United States were active during the 'Little Ice Age' (100–500 yr BP). These findings imply that fluvial activity may be more spatially restricted during warmer/drier climatic conditions than during cooler/wetter periods. We find an increase in fluvial activity during the era of Euro-American colonization (400 yr BP to present) in the southeastern United States but not the northeastern United States, implying a heterogeneous response of fluvial systems to human activities in the eastern United States related to climatic, cultural, and/or physiographic variability. These new insights gained from fluvial chronologies in the eastern United States demonstrate the utility of regionally synthesized paleo-records to understand large-scale climate variation effect on rivers. [ABSTRACT FROM AUTHOR]