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Summary This paper assesses the future variability of water resources in the short, medium and long terms over a large Sudano-Sahelian catchment in West Africa. Flow simulations were performed with a daily conceptual model. A period of nearly 50 years (1952–2000) was chosen to capture long-term hydro-climatic variability. Calibration and validation were performed on the basis of a multi-objective function that aggregates a variety of goodness-of-fit indices. The climate models HadCM3 and MPI-M under SRES-A2 were used to provide future climate scenarios over the catchment. Outputs from these models were used to generate daily rainfall and temperature series for the 21st century according to: (i) the unbias and delta methods application and (ii) spatial and temporal downscaling. A temperature-based formula was used to calculate present and future potential evapotranspiration (PET). The daily rainfall and PET series were introduced into the calibrated and validated hydrological model to simulate future discharge. The model correctly reproduces the observed discharge at the basin outlet. The Nash-Sutcliffe efficiency criterion is over 89% for both calibration and validation periods, and the volume error between simulation and observation is close to null for the overall considered period. With regard to future climate, the results show clear trends of reduced rainfall over the catchment. This rainfall deficit, together with a continuing increase in potential evapotranspiration, suggests that runoff from the basin could be substantially reduced, especially in the long term (60–65%), compared to the 1961–1990 reference period. As a result, the long-term hydrological simulations show that the catchment discharge could decrease to the same levels as those observed during the severe drought of the 1980s.