Net primary productivity (NPP) reflects the growth status of vegetation and the stability of ecosystems, which is of great significance for the sustainable development of terrestrial ecosystems and the carbon cycle of ecosystems. Based on the CASA model, this study estimated the vegetation NPP values in karst and non-karst regions from 2000 to 2021. Theil-Sen Median trend analysis and Mann-Kendall test methods were used to analyze the spatial and temporal distribution and dynamic evolution of vegetation NPP. Geographical detectors were employed to explore the main driving factors of vegetation NPP spatial differentiation in karst and non-karst regions. The results indicate that: (1) The mean annual and seasonal vegetation NPP in the karst region was higher than that in the non-karst region, with the highest NPP values in summer and the lowest in winter. The rate of increase in annual, spring, and winter vegetation NPP in the karst region was lower than that in the non-karst region, while the rate of decrease in summer was higher. (2) The average annual vegetation NPP in both karst and non-karst regions was concentrated between 500-700 gC m^-2 a^-1, showing a slow increasing trend. The ecological restoration project in the karst region was effective, with a higher proportion of areas with high vegetation NPP than in the non-karst region. The low NPP areas were mainly distributed in urban areas and along the Yangtze River, with a lower proportion in the karst region than in the non-karst region. (3) The spatial differentiation of vegetation NPP was influenced by both natural and anthropogenic factors. Air temperature, precipitation, population density, and land use type were the main driving factors for vegetation NPP changes in the karst region, while population density, land use type, elevation, and precipitation were the main driving factors in the non-karst region. There were interactive effects of dual-factor enhancement or nonlinear enhancement among the driving factors on vegetation NPP changes. The findings of this study can provide a scientific basis for regional ecological protection, ecological restoration, and sustainable development research.