This study demonstrates the use of spatially downscaled, monthly general circulation model (GCM) rainfall and temperature data to drive the established HyMOD hydrological model to evaluate the prospective effects of climate change on the fluvial run-off of the River Derwent basin in the UK. The evaluation results of this monthly hydrological model using readily available, monthly GCM data are consistent with studies on nearby catchments employing high-temporal resolution data, indicating that useful hydro-climatic planning studies may be possible using standard datasets and modest computational resources. HyMOD was calibrated against 5 km2 gridded UK Climate Projections dataset data and then driven using monthly spatially interpolated (~5 km2) outputs from Hadley Centre Coupled Model, version 3 and the Canadian Centre for Climate Modelling and Analysis for Intergovernmental Panel on Climate Change Special Report on Emissions Scenarios (IPCC-SRES) A2a and B2a covering the 2020s, 2050s and 2080s. Results for both GCMs project a decrease in annual run-off in both GCM models and scenarios with higher values in the summer/autumn months, whereas an increase in the later winter months. Both Hadley Centre Coupled Model, version 3 and the Canadian Centre for Climate Modelling and Analysis show higher ranges of uncertainty during the winter season with higher values of run-off associated with December in all three simulation periods and two scenarios. A seasonal comparison of run-off simulations shows that both GCMs give similar results in summer and autumn, whereas disparities due to GCM uncertainties are more conspicuous in winter and spring. In this study, both the GCMs under A2a scenario have demonstrated the high possibility of time shift in monthly average peak run-offs in the Derwent River by 2080s in comparison with the early 21st century. Copyright © 2013 John Wiley & Sons, Ltd.