The sensitivity and vulnerability of water resources to climate change is difficult to assess. In this study, we used a conceptual hydrologic model to investigate the sensitivity of streamflow to climate change. We also proposed a framework to evaluate the vulnerability of water resources in arid regions. We applied this framework to a case study of the Shiyang River Basin in Northwest China. Results showed that the precipitation and streamflow in Shiyang River Basin exhibited no significant trends of change from 1956 to 2010. In the past five decades, however, the temperature increased significantly by 0.37°C per decade. According to the sensitivity assessment, a 10% increase in precipitation and a 1°C increase in temperature altered mean annual streamflow by averages of 14.6% and -0.5%, respectively, from 1988 to 2005. In the 2000s, the calculated vulnerability of water resources in Shiyang River Basin was more than 0.95, indicating severe vulnerability. The increase in the amount of precipitation and the implementation of water-saving measures can reduce the vulnerability of water resources in the future; if precipitation increases by 10% per decade and the use of irrigation water decreases by 15% in the 2030s, the evaluated value of water resources vulnerability will be reduced to 0.79. However, the region remains highly vulnerable. The proposed framework for vulnerability assessment can be applied to the arid regions in Northwest China, and the results of our efforts can identify adaptation strategies and improve the management of water resources in such regions.