Integrated approaches are needed to assess the effects of global changes on the future state of water resources at regional scales. We develop a hydro-economic model of the Gállego catchment, Spain, to assess how global change and policy options affect the catchment’s water scarcity and the economic implications to the agricultural sector. The model couples physical processes (hydrology) and regulatory and economic processes (agricultural water demand, reservoir operation). Five scenarios, covering currently ongoing changes in climatic conditions, agriculture and hydrological planning, are evaluated. Our results suggest that the scenarios’ impacts on water resources and regional agricultural income are significant. Policy responses such as investments in modernization of irrigation technology would mitigate the negative impacts of climatic change on the agricultural sector, but the implementation costs outweigh the extra regional agricultural income. Also, a planned reservoir extension project appears ineffective, even considering effects of climatic change. Although our results are site-specific, our methodology is relevant to other areas that face comparable problems of water scarcity.