The vulnerability of a city is an important index to evaluate the healthy development of a city, and also an important guide to the harmonious and sustainable development of resource-based cities. This paper constructs the vulnerability assessment system of resource-based cities from four dimensions of resources, ecology, society and economy, and puts forward the Entropy Weight-TOPSIS model to study the dynamic changes of urban vulnerability in the resource-based city—Karamay. The research results show that the urban vulnerability score of Karamay rose steadily from 2008 to 2017, but the overall vulnerability score was always between 0.1 and 0.2, indicating that the urban vulnerability of Karamay has not significantly improved and is still in the stage of extremely fragile economic and social comprehensive development. The ecological vulnerability, social vulnerability and economic vulnerability of Karamay show a good trend of improvement, and social development contributes the most to the comprehensive vulnerability of the city, while the score of resource vulnerability shows a significant decline. Resource development and utilization is still the key to determine the healthy and sustainable development of Karamay.