The Hydrologic Simulation Program-FORTRAN (HSPF) model is widely used to develop management strategies for water resources. The spatial resolution of the input data used to parameterize the HSPF model may lead to uncertainty in model outputs. In this study, we evaluated the impact of the spatial resolution of the digital elevation model (DEM) and land use data on uncertainty in HSPF-predicted flow and sediment. The resolution of DEMs can affect stream length, watershed area, and average slope, while the resolution of land use data can influence the distribution of land use information. Results showed that DEMs and land use maps with finer resolutions generated higher flow volumes and sediment loads. There was a non-linear relationship between changes in resolution of the DEM and land use data and changes in the uncertainty of predicted flow and sediment loads. Relative error was used to describe model uncertainty and the probability density function was used to estimate these uncertainties. The best-fit distributions of uncertainty in modeled flow and sediment related to DEM and land use data resolution were the generalized Pareto distribution and the Johnson SB distribution, respectively. The results of this study provide useful information for better understanding and estimating uncertainties in the HSPF model.