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Abstract Despite the numerous hydrological, geological, and ecological benefits produced by floodplain landscapes, floodplains continue to be degraded by human activities at a much higher rate than other landscape types. This large-scale landscape modification has been widely recognized, yet a comprehensive, national dataset quantifying the degree to which human activities are responsible for this degradation has not previously been evaluated. In this research, we analyze floodplain integrity for the contiguous United States by spatially quantifying the impact of anthropogenic stressors on almost 80,000 floodplain units. We demonstrate the prevalence of human modifications through widely available geospatial datasets, which we use to quantify indicators of floodplain integrity for five essential floodplain functions of flood attenuation, groundwater storage, habitat provision, sediment regulation, and organics and solute regulation. Our results show that floodplain degradation is spatially heterogeneous and that the integrity of nearly 70% of floodplains in the United States is poor. We highlight that quantifying the integrity of spatially explicit floodplain elements can allow for restoration efforts to be targeted to the areas in most desperate need of preservation.