There are limited literature on the impacts of drought on crop yields in warm regions such as southwest China. Drought vulnerability of four different crops (wheat, rice, maize and sugarcane) cultivated in three provinces (Sichuan, Guizhou and Yunnan) within southwest China were investigated in this study. It was based on the drought index of standardized precipitation evapotranspiration index (SPEI) for -3- and -6 months timescales (SPEI-3 and SPEI-6). The correlation between the SPEI and the standardized yield residuals series index for the individual crops was estimated for the period from 1960 to 2018. The highest drought duration was recorded in the southern part of the study area especially in the Yunnan Province. For SPEI-3, 60% of the total area was affected by drought mainly during the months from August to December for about 13 years (2005–2018). In terms of SPEI-6, the total affected area by the drought exceeded 80% during the timeframe from 2009 to 2013. Among the studied crops, winter wheat had the highest annual crop yield losses particularly in 2010 when the loss exceeded 50%. The results of this study have implications for agricultural management and climate policymaking in minimizing the influence of drought under the warming climate in southwest China. Further, it provides greater insight into crop–climate interactions and sustainable crop production.