From the perspective of city-transport system, this article applies space syntax to analyze the physical integration of cities. Traditionally, space syntax is mainly applied to urban areas, buildings, and other scales. However, when space syntax is applied to the configuration analysis of urban agglomeration, the change of scale causes changes in spatial perception and human behavioral patterns. Thus, we present a new method of space syntax. This method defines the lane and track between entrance and exit, and city as node, which represents small-scale space. Infrastructure, such as stations, entrances, and exits, are defined as links. The urban agglomeration is thus transformed into a topological network, and then displayed as a bipartite graph of cities and routes. We take the urban agglomerations in the Yangtze River Middle Reaches (YRMR) as the case study area and analyze its spatial configuration from the perspectives of local and integral, interfaces at different scales, gaps, evolution of the dual foreground and background networks, and evolution of the transport networks. The results reveal the way cities integrate with each other and further reveal the multi-scale spatial structure of urban agglomeration.