This data release contains inputs for and outputs from hydrologic simulations of the southeastern U.S. using the Monthly Water Balance Model, the Precipitation Runoff Modeling System (PRMS), and statistically-based methods. These simulations were developed to provide estimates of water availability and statistics of streamflow for historical and potential future conditions for an area of approximately 1.16 million square miles. These model input and output data are intended to accompany a U.S. Geological Survey Scientific Investigations Report (LaFontaine and others, 2019); they include four types of data: 1) model input parameters, 2) model output statistics, 3) GIS files of the model hydrologic response units and stream segments, and 4) statistically-based streamflow estimates for headwater watersheds. LaFontaine, J.H., Hart, R.M., Hay, L.E., Farmer, W.H., Bock, A.R., Viger, R.J., Markstrom, S.L., Regan, R.S., and Driscoll, J.M., 2019, Simulation of Water Availability in the Southeastern United States for Historical and Potential Future Climate and Land-Cover Conditions: U.S. Geological Survey Scientific Investigations Report, 2019-5039, 83 p., https://doi.org/10.3133/sir20195039.