Karst areas are one of the world's major ecological fragile zones, are prone to influences from human activities and climate change. Although the vegetation cover in karst area of southwest China increased significantly in recent decades, there are obvious spatial differences in vegetation greening. To better elevate the relative importance of the anthropogenic factors and climatic factors to the vegetation greening, and explore the factors leading to the spatial heterogeneity of vegetation greening in karst desertification area where vegetation was seriously degraded, linear regression analysis, correlation analysis and residual analysis were used to evaluate the contribution of anthropic factors and climatic factors to the growth of normalized difference vegetation index (NDVI) from 1998 to 2020, and revealed the correlations between natural factors (proportion of karst areas, elevation and landscape pattern) anthropic factors (change in land use, population density and gross domestic product), climatic factors (annual temperature and annual precipitation) and the spatial-temporal variation of county NDVI in the paper. The results showed that (1) generally, the NDVI value increased by 23.59% from 1998 to 2020 in total area, and the anthropic factor dominated the process of vegetation greening (87.02%). The rapid increase of vegetation coverage occurred from 2011 to 2020, which was jointly promoted by the urbanization, economic development, increasing mean temperature and precipitation, and climate change were the main contributor (67.65%). (2) there were significant spatial heterogeneity in the NDVI, which was mainly caused by the site conditions (e.g. the proportion of karst area, landscapes pattern, mean annual temperature and precipitation) and anthropic factors (e.g. the proportion of construction land, population density and gross domestic product); the county NDVI value was negatively correlated with the proportion of karst area, cropland, grassland and construction land, population density, and gross domestic product, while it was positively correlated with the proportion of woodland, mean annual temperature and mean annual precipitation. (3) Generally, vegetation greening was faster in regions with warm and humid climate or more forestland, and lower in regions with higher average elevation and economic growth. Nevertheless, the effects of environmental factors on the vegetation greening rate varied in the different periods. The land cover pattern, population density, GDP in 2000, and the rate of urbanization and economic growth influenced vegetation growth from 2000 to 2010, while the impact of mean annual temperature and mean annual precipitation became more pronounced since 2010. The results of this study contributed to understand the importance of anthropic factors and climatic factors that affect veg-etation greening in karst rocky desertification areas in different periods, which provided deci-sion-making basis for land managers.