［Objective］ Flood disaster resilience levels of a region and the factors driving their spatial heterogeneity were measured to provide scientific support for enhancing regional disaster resistance and achieving sustainable quality development. ［Methods］ Using the CRITIC-entropy weight combination and a geographic detector， a comprehensive evaluation index for flood disaster resilience was constructed using four dimensions： society， economy， infrastructure， and environment. Spatiotemporal evolution and driving factors of the spatial heterogeneity of flood disaster resilience in the middle reaches of the Yangtze River from 2012 to 2022 were analyzed. ［Results］ ① From 2012 to 2022， flood resilience in the middle reaches of the Yangtze River fluctuated and increased from 0.209 1 to 0.262 9， with only a slight decline in 2020. The structure of flood resilience evolved from ‘environment-society-infrastructure-economy’ to ‘environment-society-economy-infrastructure’. ② Significant differences in flood disaster resilience were observed within the region， with 95.24% of areas exhibiting fluctuating growth. Ganzhou and Ji’an were identified as continuously growing regions. Social resilience differences within the region gradually narrowed. Except for the Enshi and Xiangxi Prefectures， the economic resilience of other areas improved. The infrastructure resilience levels increased in 25 cities and prefectures. Environmental resilience in the northwestern part of the region was better than that in other areas. ③ The results of factor detection showed that the main factors influencing the spatial differentiation of flood resilience in 2012 were population density， terrain relief， and slope. By 2022， these factors had shifted to the number of people receiving minimum living security， the number of large-scale industrial enterprises， and the end-of-year highway mileage. ④ The results of interaction factor detection showed that the most influential interaction factors in 2012 were population density and the ∩ proportion of the tertiary industry. By 2022， it had evolved to per capita GDP ∩ end-of-year highway mileage. ［Conclusion］ The successful experiences in urban flood prevention and disaster reduction should be summarized and promoted. Dynamic monitoring of various influencing factors should be strengthened. Risk assessments should be conducted for unstable factors， and urban development strategies should be adjusted in a timely manner.