Vulnerability assessment has become a critical issue and an important approach for regional sustainable development. The Qinghai Province, located in the northeastern part of the Qinghai-Tibet Plateau, suffers a severe grassland degradation caused by climate change and human activities. The degradation constrains the development of local animal husbandry and further affects the vulnerability of social system. In this study, based on the vulnerability assessment framework of exposure-sensitivity-adaptability, two index systems were established including ecological and social aspects. The entropy weight method was used to determine the index weight. The dynamic changes of the ecological vulnerability and social vulnerability of Qinghai province were assessed from 1995 to 2015. Results indicated that ecological vulnerability in Qinghai province increased from eastern part to the west, and decreased from northern to southern part, while social vulnerability showed an opposite trend. Key ecologically fragile areas were mainly located in the Qaidam Basin and western Three-River Headwaters Region (TRHR), while key social vulnerability areas were mainly distributed in the Qilian Mountains and eastern Qinghai province. The overall ecological vulnerability showed a decreasing trend through time, but increased in several local areas. Social vulnerability dropped significantly, especially in the eastern part of Qinghai province. The results will help to identify key vulnerable areas of Qinghai province and provide references for the ecological protection and restoration and the formulation of ecosystem management policies.