The population, property and infrastructure are highly concentrated in Yangtze River Delta City Cluster, which makes it more and more sensitive to storm and flood. Therefore, the assessment of vulnerability to flood disasters is the basis for ensuring regional integration and sustainable development of the Yangtze River Delta. In this paper, 27 central cities in the Yangtze River Delta are selected. Super efficiency DEA model is applied to build urban flood vulnerability assessment model, in which flood vulnerability is considered as a negative “production”. And then the spatial differentiation analysis is carried out by using the Moran’s I and Theil index. Finally, the Tobit regression model is used to analyze the influencing factors of urban flood vulnerability. The results show that the overall urban flood vulnerability of Yangtze River Delta City Cluster varies greatly. Vulnerability in Anhui and Zhejiang is much higher than that in Jiangsu and Shanghai. From the spatial perspective, the vulnerability distribution of urban flood disasters in the Yangtze River Delta City Cluster presents obvious regional aggregation characteristics. The cities with high vulnerability are distributed in the southeast coastal area of Zhejiang and southern hilly area of Anhui. Rainfall, urban development level, and the supporting infrastructure have significant impacts on the vulnerability of urban floods. The results reveal the spatial and temporal differences of flood resilience within the Yangtze River Delta City Cluster, as well as the influence of climate factors, urban hydrology and infrastructure on urban flood disaster vulnerability. It can provide reference for improving resilience to flood disaster and promoting integrated disaster prevention and reduction.