Based on runoff, air temperature, and precipitation data from 1960 to 2010, the effects of climate change on water resources in the arid region of the northwestern China were investigated. The long-term trends of hydroclimatic variables were studied by using both Mann-Kendall test and distributed-free cumulative sum (CUSUM) chart test. Results indicate that the mean annual air temperature increases significantly from 1960 to 2010. The annual precipitation exhibits an increasing trend, especially in the south slope of the Tianshan Mountains and the North Uygur Autonomous Region of Xinjiang in the study period. Step changes occur in 1988 in the mean annual air temperature time series and in 1991 in the precipitation time series. The runoff in different basins shows different trends, i.e., significantly increasing in the Kaidu River, the Aksu River and the Shule River, and decreasing in the Shiyang River. Correlation analysis reveals that the runoff in the North Xinjiang (i.e., the Weigan River, the Heihe River, and the Shiyang River) has a strong positive relationship with rainfall, while that in the south slope of the Tianshan Mountains, the middle section of the north slope of the Tianshan Mountains and the Shule River has a strong positive relationship with air temperature. The trends of runoff have strong negative correlations with glacier coverage and the proportion of glacier water in runoff. From the late 1980s, the climate has become warm and wet in the arid region of the northwestern China. The change in runoff is interacted with air temperature, precipitation and glacier coverage. The results show that streamflow in the arid region of the northwestern China is sensitive to climate change, which can be used as a reference for regional water resource assessment and management.