Under the double stress of global climate change and human activities, the fragile ecosystem in arid desert region of Northwest China has undergone profound changes. Thus, how to evaluate the ecological vulnerability of the arid land has become a hot topic in the field of ecology. Fully considering the characteristics of the eco- environment (desertification, salinization, wind erosion, drought and other disasters) in the study area, we introduced extreme climate event factors (indicating the climate changes) and large-scale landscape pattern indexes (indicating the disturbance of human activities on the ecological landscape) to establish the evaluation system of ecological vulnerability in arid desert region of Northwest China. Then, the spatial-temporal change of ecological vulnerability and its driving mechanism during the past 13 years were analyzed and discussed. The results showed that: the ecological vulnerability of arid desert region in Northwest China generally belonged to the level of moderate or severe vulnerability, and the spatial distribution pattern of ecological vulnerability showed a decreasing trend from east to west and aEpattern appeared in the western part, which was significantly affected by the atmospheric circulation and special landform ofTwo basins sandwiched with three mountains. During the period of 2000- 2013, the ecological vulnerability in the arid desert region of Northwest China showed a decreasing trend, and the changes were greatly affected by temperature, precipitation and human activities. There were significant relationships between the change intensity of ecological vulnerability and climatic tendencies of precipitation and temperature. The research results can provide decision supports for ecological protection and management in arid desert region of Northwest China.