[Objective] The temporal and spatial evolution characteristics of ecological sensitivity in a typical coal mine resource city (Liupanshui City in Guizhou Province) in a karst region from 2000 to 2020 were analyzed in order to provide a basis for the ecological protection of coal mine resource cities in karst regions.[Methods] We chose a remote sensing ecological index, a water loss and soil erosion sensitivity index, a rocky desertification sensitivity index, a landscape development intensity index, and an index of carbon emissions to build an integrated ecological sensitivity index, and analyzed the ecological sensitivity of Liupanshui City with the aid of spatial autocorrelation analysis.[Results] ① From 2000 to 2020, the extremely sensitive, highly sensitive, mildly sensitive, and moderately sensitive areas in Liupanshui City showed a trend of fluctuation and decline, while the insensitive areas continued to rise. The ecological environment of Liupanshui City improved significantly over time. ② From 2000 to 2020, the spatial evolution trend of extremely sensitive and highly sensitive areas in Liupanshui City was scattered over the entire city, shifted to the southeast, and spread to the northwest, and the area continued to shrink. Except for the slight spread in the south of Zhongshan District, other areas showed a continuous or fluctuating shrinking trend, and the environment tended to improve. ③ From 2000 to 2020, the Global Moran's I values for Liupanshui City were 0.525, 0.570 and 0.476, respectively, indicating that the ecological sensitivity of Liupanshui City had a positive spatial correlation, and the correlation gradually weakened with time. The LISA diagram showed that the high and low aggregation areas decreased, and the degree of ecological sensitivity aggregation decreased.[Conclusion] The ecological sensitivity of Liupanshui City is mainly mild, mainly distributed in the northwest region with better ecological conditions. The proportion of extremely sensitive areas was small, concentrated in the southeast where the natural conditions are more fragile. With the passage of time, afforestation and other engineering measures in Liupanshui City have alleviated the environmental deterioration caused by excessive human intervention to a certain extent, reducing the area of extremely sensitive and highly sensitive areas in the region and significantly improving the ecological environment.