Abstract: Flow space has become an important content in the study of urban agglomeration spatial structure, and how to identify the characteristics of urban agglomeration flow space structure and reveal its impact on the physical space of urban agglomerations is the focus and difficulty of current urban agglomeration spatial structure research. This paper uses the data of enterprises’ off-site investment in 1992, 2001, 2010, and 2019 to construct a city connection network in the Yangtze River Delta. With the help of complex network analysis, K-means clustering and other analysis methods, it explores the evolution of the overall characteristics of the regional economic network and analyzes the evolution law of the network spatial organization structure. The results show that: (1)From 1992 to 2019, the intensity of urban connection in the Yangtze River Delta has increased significantly, and the degree of dispersion and imbalance in the importance and influence of urban nodes has been shrinking. The urban economic networks features small-world network properties more prominently, and the scale-free characteristics are gradually weakening. (2)The urban economic network in the Yangtze River Delta has changed from “V-shaped” structure to the polygonal network structure of interconnected core cities; the network connection has expanded from the interconnection among core cities to the connection among the core city and its surrounding neighboring cities. Spatial proximity network connection features begin to emerge; the participating cities in the network system gradually expanded from core cities to the whole region, and core cities such as Nanjing, Hangzhou, and Hefei formed a relatively independent external radiation network system. (3)The urban hierarchy in the Yangtze River Delta has formed a pyramid structure, with Shanghai as the core city being the most prominent; Hangzhou and Nanjing are the second; Ningbo, Hefei, Shaoxing, Suzhou, Wuxi, Jiaxing and other cities are the third. (4)The development and evolution of the urban economic network in the Yangtze River Delta has gradually moved from the initial development stage and the hierarchical stage to the network stage.