Despite consensus that impervious surfaces increase flooding, the magnitude of the increase remains uncertain. This uncertainty largely stems from the challenge of isolating the effect of changes in impervious cover separate from other factors that also affect flooding. To control for these factors, prior study designs rely on either temporal or spatial variation in impervious cover. We leverage both temporal and spatial variation in a panel data regression design to isolate the effect of impervious cover on floods. With 39 years of data from 280 U.S. streamgages, we estimate that a one percentage point increase in impervious basin cover causes a 3.3% increase in annual flood magnitude (95%CI: 1.9%, 4.7%) on average. Using 2,109 streamgages, some of which have upstream regulation and/or overlapping basins, we estimate a larger effect: 4.6% (CI: 3.5%, 5.6%). The approach introduced here can be extended to estimate the causal effects of other drivers of hydrologic change.