Drought poses significant threats to ecosystem stability, particularly in fragile karst landscapes. Guangxi Zhuang Autonomous Region, located in a subtropical monsoon climate zone, faces unique drought challenges despite its humid climate. Seasonal monsoon shifts and complex topography drive spatially heterogeneous precipitation patterns, resulting in frequent spring and autumn droughts. These droughts are exacerbated in karst areas, where thin soil layers and poor water retention capacity trigger transient but severe moisture deficits, threatening the stability of karst ecosystem. While extensive research has focused on drought impacts in arid/semiarid northern China, where vegetation is perennially water-limited, mechanisms underlying drought-vegetation interactions in humid southern regions remain poorly understood. To address these gaps, we focus on Guangxi Zhuang Autonomous Region and investigate the contribution of multi-scale meteorological drought to Normalized Difference Vegetation Index (NDVI) changes, revealing vegetation response differences between karst and non-karst areas in southern China. Using monthly Standardized Precipitation Evapotranspiration Index (SPEI) and NDVI data from 2001 to 2020, we applied trend analysis and ridge regression to quantitatively evaluate the contribution of multi-scale SPEI to vegetation changes and their geomorphic differentiation. The results showed: (1) Over the past 20 years, vegetation NDVI in Guangxi significantly increased at a rate of 0.005 a–1 (P<0.05), with a higher growth rate in karst areas than in non-karst areas. Meteorological drought is predominantly characterized by short-term (1—6 months) drought conditions, while long-term (12—24 months) SPEI shows a trend towards wetter conditions. The combined effects of these characters drive vegetation changes. (2) The response of vegetation to SPEI at different scales varies significantly. Increases in the 3-, 12-, and 24-month SPEI result in NDVI growth. However, an increase in the 6-month SPEI may lead to soil moisture oversaturation, which suppresses root respiration and results in a decline in NDVI. In over 70% of Guangxi, the response of NDVI to SPEI is dominated by the 12- and 24-month scales, contributing to annual NDVI increases of 0.011 a–1 and 0.015 a–1, respectively. (3) Shallow-rooted vegetation (e.g., savannas and grasslands) in karst areas was particularly sensitive to 3—6-month droughts, whereas vegetation in non-karst areas was primarily regulated by long-term (12—24-month) SPEI changes. These findings highlight the necessity for differentiated drought adaptation: karst regions require early warnings for 3—6-month droughts and restoration of shallow-rooted vegetation to enhance resilience, while non-karst regions should prioritize long-term water balance management to mitigate ecological risks from prolonged moisture shifts. By bridging the knowledge gap in multi-scale drought contributions and geomorphic-specific vegetation responses, this study provides a scientific foundation for ecosystem conservation and climate adaptation in humid southern China.