Resource depletion, land-use change, and population growth triggered by the industrial revolution represent serious issues shared globally that have altered the structure, processes, and functions of ecosystems and had significant impacts on human well-being and survival security. This paper assesses changes in ecosystem service values (ESVs) in karst areas based on the perspective of land-use change. Guizhou province, which is typical of the South China Karst (SCK) ecologically fragile areas, was taken as a research subject. The past, current, and future spatial-temporal evolution of karst ESVs were assessed, using equivalence factors and CA-Markov modelling methods. The results show that: (1) from 1980 to 2040, arable land, woodland, and grassland occupy the main land types in the study area; at the same time, the water and built-up areas show a steady growth trend, with dramatic land use shifts occurring in the western, middle, and northern parts. (2) The overall ESVs increased by US$ 31.12 million during the study period, showing a temporal change trend of first decreasing and then increasing; forest land, grassland, and arable land area shift are the main factors of ESVs change; soil conservation, biodiversity conservation, and gas regulation functions are enhanced and play a vital role in the single ESVs increase; ESVs show a basin-type spatial distribution pattern. (3) The sensitivity index is <1, the ESV is inelastic to the VC factor adjustment, and the results are true and valid. This paper found that using quantitative methods to predict land use change of the South China Karst can provide accurate assessment of the differences in supply and demand for natural and social ecosystem services (ES) in a region, clarifying the trade-offs and synergies of ecosystem service functions, contributing to the achievement of sustainable development, and providing a practical reference for global land landscape optimization and land resource planners.