Changes in water resources availability can be expected as consequences of climate change, population growth, economic development and environmental considerations. A two-stage modeling approach is used to explore the impact of these changes in the Middle East and North Africa (MENA) region. An advanced, physically based, distributed, hydrological model is applied to determine the internal and external renewable water resources for the current situation and under future changes. Subsequently, a water allocation model is used to combine the renewable water resources with sectoral water demands. Results show that total demand in the region will increase to 393 km3 yr−1 in 2050, while total water shortage will grow to 199 km3 yr−1 in 2050 for the average climate change projection, an increase of 157 km3 yr−1. This increase in shortage is the combined impact of an increase in water demand by 50% with a decrease in water supply by 12%. Uncertainty, based on the output of the nine GCMs applied, reveals that expected water shortage ranges from 85 km3 yr−1 to 283 km3 yr−1~in 2050. The analysis shows that 22% of the water shortage can be attributed to climate change and 78% to changes in socio-economic factors.