Study region: The Bas-Loukkos catchment, a Mediterranean catchment in northern Morocco exposed to growing water withdrawal caused mainly by agricultural development. Study focus: For adaptation to climate change, water managers have to consider the high and various uncertainties. To assess impacts of climate change on projected water resources, this study aimed to develop a smart analysis framework to provide scientific information by exploring the complexity of many projections combined with hydrological models. Uncertainties were quantified using 13 pair-wise combinations of 5 regional climate models forced by 4 global climate models under two emissions scenarios (RCP4.5 and RCP8.5), data with and without bias correction (using empirical quantile mapping), and two sets of GR2M hydrological model parameters corresponding to different precipitation conditions. The Budyko hypothesis was used to analyse combined effects of climate change on water resources according to water-withdrawal scenarios. Climate and hydrological projections have been analyzed over three periods: short-term [2020–2040], medium-term [2041–2060] and long-term [2081–2100]. New hydrological insights for the region: Results from all simulations indicate that, in the long term (2081–2100), precipitation and discharge will decrease by ca. 21–38% and ca. 50–71%, respectively, compared to the reference period (1981–2005). Consequently, this decline in water resources will require water management strategies to adapt to the future climatic conditions and water demand.