[Objective] Since the beginning of the 21st century, the frequent occurrence of extreme drought events in southwest China has had a serious negative impact on vegetation growth. It is of great significance to study the response mechanism of vegetation to drought at different time scales.[Methods] Based on vegetation net primary productivity (NPP) data with a spatial resolution of 500m from 2001 to 2019 and standardized precipitation Evapotranspiration index (SPEI) data on a continuous scale from 1–24 months in Southwest China, Correlation analysis, maximum synthesis method and significance test were used to analyze the responses of NPP of different geomorphic types and vegetation types to multi-scale SPEI in Southwest China.[Results] (1) In the annual scale, seasonal scale and growing season, the responses of vegetation NPP and SPEI at 1-24 months are dominated by the January-March scale, and vegetation NPP has a good response to short-term drought changes, but a relatively poor response to medium and long-term drought changes. (2) The response of NPP to SPEI at 1-24 month scale showed significant spatial heterogeneity and seasonal differences. The correlation between NPP and SPEI at 1-24 month scale in summer was significantly negative in the five major geomorphic regions. The response area of NPP in spring to SPEI at July-September scale was larger than that in other seasons. The area of vegetation NPP positively correlated with SPEI from 1 to 24 months in autumn and winter was larger, reaching 72% and 79.4%, respectively. In the correlation analysis between vegetation NPP and SPEI from 1 to 24 months in growing season, the area with the largest positive correlation was Guangxi Hills, while the area with the largest negative correlation was Hengduan Mountain. (3) The responses of NPP to SPEI from 1–24 months were different among different vegetation types. Although the response characteristics of grassland, scrub and forest land to SPEI were basically similar, the trend of negative correlation between NPP and SPEI became stronger with the scales of SPEI decreased in summer for all types of vegetation. This suggests that all types of vegetation are more susceptible to drought under high temperature and drought conditions in summer.[Conclusion] The research results provide effective scientific support for the protection and restoration of the ecosystem in Southwest China, and provide important theoretical basis for disaster prevention and reduction and coping with climate change, and help formulate more targeted policies and measures to promote the sustainable development of Southwest China.