Objectives The middle and lower reaches of the Yangtze River, including Hubei, Hunan, Jiangxi, Anhui, Jiangsu, Zhejiang and Shanghai, are important planting bases of commercial grain in China. However, at present, there are relatively few studies on agricultural drought in this region, and there is a lack of attention to the response of land cover types to drought. Moreover, in the context of climate change, the evolution and trend of agricultural drought in the middle and lower reaches of the Yangtze River need further discussion. Methods This study used MODIS (moderate resolution imaging spectroradiometer) V6 products to construct vegetation condition index (VCI), temperature condition index (TCI) and vegetation health index (VHI) to monitor the temporal and spatial evolution of agricultural drought in the middle and lower reaches of the Yangtze River from 2001 to 2019, and further explored the drought sensitivity of different vegetative types.Based on the concept of climate change, this study analyzed the drought trends in six provinces and one city in the middle and lower reaches of the Yangtze River. The results of the above three indices were further evaluated by standardized precipitation index (SPI) on different time scales, obtained and calculated from the CHIRPS V2.0 dataset. Results The results show that the VCI and TCI could monitor the long-term abnormal vegetation growth and heat anomalies, respectively, but neither index could provide comprehensive overview of drought conditions. Combining the advantages of both indices with the weights of 0.7 and 0.3 for VCI and TCI, respectively, the VHI, was more effective in agricultural drought monitoring in the middle and lower reaches of the Yangtze River. Different vegetation showed different drought sensitivity in study. Crops have the highest sensitivity to drought, forests are the lowest, and grasslands are somewhere in between. In the context of climate change, Jiangxi, Hunan, Hubei, Zhejiang, and Anhui show an intense wet trend in the past 20 years, while the Jiangsu and Shanghai show a weak wet trend. Conclusions Drought indices should be integrated to provide comprehensive evaluation of agricultural drought in the middle and lower reaches of the Yangtze River. Jiangsu province and Shanghai city are still at drought risk due to the weak wet trend and the local agricultural department should take drought mitigation measures to prevent economic losses. In the middle and lower reaches of the Yangtze River, croplands have the most obvious response to drought, indicating that crops are most sensitive to drought than grasses and forests, more attention should be paid to agriculture management. The relevant results can provide reference for the early warning of drought in various provinces and cities in the middle and lower reaches of the Yangtze River and help the management of regional agricultural production.