Drought is one of the major meteorological disasters in China. In the context of global warming, the losses caused by drought have increased significantly. As an important grain, edible oil, and cotton production area, the Middle and Lower Yangtze Basin is densely populated and economically developed. Although the area is rich in water resources, the temporal distribution of precipitation is uneven and interannual variation is large, which often induces terrible seasonal drought. Based on daily temperature and precipitation data of 129 stations in the Middle and Lower Yangtze Basin, the Standardized Precipitation Evapotranspiration Index (SPEI) was used to analyze the trends, stations proportions, severity, and frequency of annual and seasonal droughts. The relationships between drought and temperature, precipitation, and ENSO (El Niño-Southern Oscillation) were also considered. The regional analysis of SPEI indicated that annual, spring and autumn droughts have become more serious, especially in spring; summer and winter showed a wetter trend. For annual drought, the Han River Basin, Midstream River area, and Dongting Lake Basin were increasingly dry, whereas the Poyang Lake Basin,Downstream River area, and Taihu Lake Basin mainly showed a decreasing trend. For the stations, 96.90% and 92.25% showed a drought trend in the spring and autumn, respectively; 82.95% and 72.87% of stations showed a wetting trend in summer and winter, respectively. The station's proportions and severity of annual, spring, and autumn droughts all showed an increasing trend. In spring, these trends are significant, while the proportion and severity of summer and winter droughts all showed a decreasing trend. Annual and spring drought frequency peaked at the beginning of the 21st century. Frequency of annual, spring, and summer droughts increased from the 1990s to the beginning of the 21st century. The drought trends of spring and autumn are related to decreases in precipitation and increases in temperature, with the increase in precipitation contributing to the wet trends in summer and winter. There is significant correlation between the spring drought and SOI (Southern Oscillation Index) of last winter. If a La Nina event occurred in winter, the next spring would be increasingly prone to drought.