This paper explores the predicted hydrologic responses associated with the compounded error of cascading global circulation model (GCM) uncertainty through hydrologic model uncertainty due to climate change. A coupled groundwater and surface water flow model (GSFLOW) was used within the differential evolution adaptive metropolis (DREAM) uncertainty approach and combined with eight GCMs to investigate uncertainties in hydrologic predictions for three subbasins of varying hydrogeology within the Santiam River basin in Oregon, USA. Predictions of future hydrology in the Santiam River include increases in runoff in the fall and winter months and decreases in runoff for the spring and summer months. One-year peak flows were predicted to increase whereas 100-year peak flows were predicted to slightly decrease. The predicted 10-year 7-day low flow decreased in two subbasins with little groundwater influences but increased in another subbasin with substantial groundwater influences. Uncertainty in GCMs represented the majority of uncertainty in the analysis, accounting for an average deviation from the median of 66%. The uncertainty associated with use of GSFLOW produced only an 8% increase in the overall uncertainty of predicted responses compared to GCM uncertainty. This analysis demonstrates the value and limitations of cascading uncertainty from GCM use through uncertainty in the hydrologic model, offers insight into the interpretation and use of uncertainty estimates in water resources analysis, and illustrates the need for a fully nonstationary approach with respect to calibrating hydrologic models and transferring parameters across basins and time for climate change analyses. Copyright © 2012 John Wiley & Sons, Ltd.