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Quantitatively revealing the response of carbon stocks to land use change (LUCC) and analyzing the vulnerability of ecosystem carbon stock (ECS) services are of great significance for maintaining the carbon cycle and ecological security. For this study, China's Guizhou Province was the study area. Land use data in 2000, 2010, and 2020 were selected to explore the impacts of LUCC on carbon stocks in multiple scenarios by combining the PLUS and InVEST models and then analyzing the vulnerability of ECS services. The results show that forest land plays an important role in improving ECS services in karst plateau mountainous areas. In 2000–2020, forest land expansion offset the carbon stock reduced by the expansion of built-up land, greatly improving the regional ECS function. Following the natural trend (NT), the total carbon stock in Guizhou Province will decrease by 1.86 Tg; however, under ecological protection (EP) measures, the ECS service performs a positive function for LUCC. Focusing on socioeconomic development (ED) will increase the vulnerability of the regional ECS service. In the future, the forest land area size should be increased, and built-up land should be restricted to better improve the service function of ECS in karst plateau mountainous areas. [ABSTRACT FROM AUTHOR]