This study investigated the effect of increasing population and changing climatic conditions on the water resources of a semi-arid region, the Las Vegas Valley (LVV) in southern Nevada. A system dynamics model was developed for the LVV from 1989 to 2035. The impact of climate change on water demand and the water supply from the Colorado River was modeled, using projections from 16 global climate models for 3 emission scenarios. Variability in water demand and supply under different scenarios of population growth and demand management, including water conservation and water pricing, was evaluated. With the population growth that was projected, if no further demand management policies were implemented, the LVV would not be able to meet the water demand in the near future. However, by combining water conservation and pricing policies, the available supply could last well into the future. The reduction in water demand in 2035 was predicted to be 327 million cubic meters (MCM) for 'status quo' population growth, or 30.6%; 408 MCM for 50% of the projected growth, or 38%; and 511 MCM for no population growth, or 47.8%. Water supply reliability decreased significantly with changing climatic conditions. Therefore, major challenges to water sustainability in the LVV would be due to rapid population growth as well as to climate variability. However, with the combination of reduced population growth rate and water conservation policies, the Colorado River supply could meet the future demand of the LVV most of the time.