As a result of inappropriate management and rising levels of societal demand, in arid and semi-arid regions water resources are becoming increasingly stressed. Therefore, well-established insight into the effects of climate change on water resource components can be considered to be an essential strategy to reduce these effects. In this paper, Iran's climate change and variability, and the impact of climate change on water resources, were studied. Climate change was assessed by means of two Long Ashton Research Station-Weather Generator (LARS-WG) weather generators and all outputs from the available general circulation models in the Model for the Assessment of Greenhouse-gas Induced Climate Change-SCENario GENerator (MAGICC-SCENGEN) software, in combination with different emission scenarios at the regional scale, while the Providing Regional Climates for Impacts Studies (PRECIS) model has been used for projections at the local scale. A hydrological model, the Runoff Assessment Model (RAM), was first utilized to simulate water resources for Iran. Then, using the MAGICC-SCENGEN model and the downscaled results as input for the RAM model, a prediction was made for changes in 30 basins and runoffs. Modeling results indicate temperature and precipitation changes in the range of ±6 °C and ±60%, respectively. Temperature rise increases evaporation and decreases runoff, but has been found to cause an increased rate of runoff in winter and a decrease in spring.