Drought stress threatens vegetation dynamics across diverse ecosystems. Monitoring how vegetation responds to water stress is vital for ecological conservation. The response of vegetation photosynthesis to water availability variations in Southwest China from 2008 to 2018 is investigated in this study. The solar-induced fluorescence (SIF) derived from GOME-2 is used to characterize photosynthetic changes. We examined the sensitivity of SIF anomaly to standardized precipitation-evapotranspiration index (SPEI) at multiple time scales to evaluate the drought impacts on different ecosystems (i.e. forests, croplands, grasslands, and shrublands). We find that (1) SIF has significant yet weak correlations to SPEI across major ecosystems in Southwest China; (2) Forests are more sensitive to short-term droughts in comparison with other ecosystems. (3) Cropland, grassland, and shrubland are more subjected to long-term droughts compared to forests. Our findings indicate that, in Southwest China, satellite SIF may not be effective in monitoring the impact of drought on vegetation due to its weak response to SPEI. The robustness of using satellite-observed SIF to assess drought’s effects still needs to be further tested with high-resolution SIF data.