The flood grades in provinces in the middle and lower reaches of Yangtze River (MLYR) from 1991 to 2020 are evaluated based on the Chinese Flood Damage Assessment Standard (SL579-2012). The spatiotemporal variation of flood disasters and the influencing factors are analyzed using the Mann-Kendall trend test, R/S method and random forest method. The results showed that, from the temporal perspective, the flood loss rates and flood grades decreased in provinces in the MLYR from 1991 to 2020. The flood control and disaster reduction capacity of the MLYR was significantly improved. From the spatio perspective, the flood disasters in the middle Yangtze River (MYR) were higher than the lower Yangtze River (LYR), and that on the south side of the MLYR were higher than the values on the north side of the MLYR. The mutation points of flood grades in Hubei, Hunan and Jiangxi provinces in the MRY occurred in 1998. The mutation points of flood grades in Anhui, Jiangsu and Zhejiang provinces of the LRY occurred in 2007. The flood grades in the MLYR were positively influenced by precipitation, and negatively influenced by socio-economic, natural resources and disaster prevention and mitigation capabilities. The flood grades in Hubei, Jiangxi, Jiangsu, Zhejiang provinces and Shanghai municipality were mainly affected by precipitation and disaster prevention and mitigation capabilities. The flood grades in Hunan and Anhui provinces were mainly affected by precipitation and cultivated area.