Understanding the relationship between urban form and structure and spatial variation of property flood risk has been a longstanding challenge in urban planning and city flood risk management. Yet limited data-driven insights exist regarding the extent to which variation in spatial inequality of property flood risk in cities can be explained by heterogenous features of urban form and structure. In this study, we explore eight key features (i.e., population density, point of interest density, road density, minority segregation, income segregation, urban centrality index, gross domestic product, and human mobility index) related to urban form and structure to explain variability in spatial inequality of property flood risk among 2567 US counties. Using rich datasets related to property flood risk, we quantify spatial inequality in property flood risk and delineate features of urban form and structure using high-resolution human mobility and facility distribution data. We identify significant variation in spatial inequality of property flood risk among US counties with coastline and metropolitan counties having the greatest spatial inequality of property flood risk. The results also reveal variations in spatial inequality of property flood risk can be effectively explained based on principal components of development density, economic activity, and centrality and segregation. Using a classification and regression tree model, we demonstrate how these principal components interact and form pathways that explain levels of spatial inequality in property flood risk in US counties. The findings offer important insights for the understanding of the complex interplay between urban form and structure and spatial inequality of property flood risk and have important implications for integrated urban design strategies to address property flood risk as cities continue to expand and develop.