A sound ecosystem is the prerequisite for the sustainable development of human society, and the karst ecosystem is a key component of the global ecosystem, which is essential to human welfare and livelihood. However, there remains a gap in the literature on the changing trend and driving factors of ecosystem services value (ESV) in karst areas. In this study, Guizhou Province, a representative region of karst mountainous areas, was taken as a case to bridge the gap. ESV in the karst areas was predicted, based on the land use change data in 2009–2018, and the driving mechanisms were explored through the gray correlation analysis method. Results show that a total loss of CNY 21.47 billion ESV from 2009 to 2018 is due to the conversion of a total of 22.566% of the land in Guizhou, with forest land as the main cause of ESV change. By 2025 and 2030, the areas of garden land, water area, and construction land in Guizhou Province will continue to increase, whereas the areas of cultivated land, forest land, and garden land will decline. The total ESV shows a downward trend and will decrease to CNY 218.71 billion by 2030. Gray correlation analysis results illuminate that the total population and tertiary industry proportion are the uppermost, among all the driving factors that affect ESV change. The findings in this study have important implications for optimizing and adjusting the land use structure ecological protection and will enrich the literature on ESV in ecologically fragile areas.