•Hydrological processes are recurrently affected by land-use and climate changes.•Synthetic experiments with advanced models can explain some feedback mechanisms.•Alterations in the hydrological response depends on the basins’ spatial scale.•Urbanization and its spatial evolution affect the runoff components partitioning.•Urbanization could either smooth or exacerbate climate change effects on runoff. This paper proposes a modeling framework able to analyze the alterations in watershed hydrology induced by two recurrent drivers for hydrological changes: climate change and urbanization. The procedure is based on the coupling of a stochastic weather generator with a land use change model for the generation of some hypothetical scenarios. The generated scenarios are successively used to force a physically-based and spatial distributed hydrological model to reconstruct the basin response under different conditions. Several potential climate alterations are simulated by imposing negative and positive variations in the mean annual precipitation and a simultaneous temperature increase. Urbanization is conceptualized by an increase in the impervious fraction of the basin. The procedure is applied to a large basin and a much smaller sub-basin; the results show how climate and land use changes may interact and affect the fundamental hydrological dynamics and how the processes governing basin hydrological response may change with spatial scale.