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Due to the special nature of karst landforms, quantification of their vegetation dynamics and their underlying driving factors remains a formidable challenge. Based on the NDVI dataset, this study uses principal component analysis to extract comprehensive factors and utilizes an optimized parameter-based geographical detector and geographically weighted regression models to assess the explanatory capacity of comprehensive factors concerning the spatial differentiation of vegetation change. The results of this study revealed the following: (1) In terms of temporal and spatial vegetation changes, the Asian karst concentrated distribution area (AKC) displayed overall stability and an increasing trend between 2000 and 2020. Notably, the northern (Southwest China) karst region experienced the most substantial vegetation increase, with increased areas exceeding 70%, primarily concentrated in the provinces of Guizhou and Guangxi. In contrast, the southern (Indochina Peninsula) karst region, particularly in Cambodia, Laos, and Vietnam (CLV), exhibited a significant decreasing trend, with decreased areas exceeding 30%. (2) By analyzing the driving factors affecting vegetation change, vegetation changes exhibited distinct spatial differentiations, along with positive and negative effects. Human factors, including human activity intensity, urban economic development, and agricultural economic development (explanatory power and local R² were both greater than 0.2), exerted a more significant impact on vegetation change in the AKC than natural factors such as thermal conditions, water conditions, and soil conditions. This impact was positive in Southwest China but inhibited in the Indochina Peninsula, particularly within the CLV karst area. Notably, the interaction between natural and human factors greatly enhanced their impacts on vegetation changes. These results provide valuable insights into vegetation changes and their driving mechanisms, which are crucial for preserving the stability of delicate karst ecosystems and facilitating vegetation recovery. Full article