This study investigates the spatial dependence of house prices in the Yangtze Delta Urban Agglomeration since the year 2000. According to Moran’s I index and the LISA scatter plot derived from a cross-section data set, the spatial dependence of house prices can be traced across the 25 cities in the agglomeration and became more evident after 2005. This study develops a spatial panel model with geographical distance and economic distance weight matrices. Spatial effects significantly influenced house prices in both cases but the intensity of the former was weaker than for the latter. Income, proportion of the tertiary industry, and amenity exhibited significant indirect effects on house prices in other cities in the inner region of the agglomeration, while competition of population between cities with economic proximity exerted negative indirect effects. Furthermore, urban industrial structure, innovation capability, and urbanization degree revealed differences in terms of spatial dependence among various city groups.