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Runoff in the United States is changing, and this study finds that the measured change is dependent on the geographic region and varies seasonally. Specifically, observed annual total runoff had an insignificant increasing trend in the US between 1950 and 2010, but this insignificance was due to regional heterogeneity with both significant and insignificant increases in the eastern, northern, and southern US, and a greater significant decrease in the western US. Trends for seasonal mean runoff also differed across regions. By region, the season with the largest observed trend was autumn for the east (positive), spring for the north (positive), winter for the south (positive), winter for the west (negative), and autumn for the US as a whole (positive). Based on the detection and attribution analysis using gridded WaterWatch runoff observations along with semi-factorial land surface model simulations from the Multi-scale Synthesis and Terrestrial Model Intercomparison Project (MsTMIP), we found that while the roles of CO2 concentration, nitrogen deposition, and land use and land cover were inconsistent regionally and seasonally, the effect of climatic variations was detected for all regions and seasons, and the change in runoff could be attributed to climate change in summer and autumn in the south and in autumn in the west. We also found that the climate-only and historical transient simulations consistently underestimated the runoff trends, possibly due to precipitation bias in the MsTMIP driver or within the models themselves.