Abstract: The Guangzhou-Shenzhen cooperation is of great significance for serving the construction of the Guangdong-Hong Kong-Macao Greater Bay Area and promoting coordinated regional development. The special significance of the Guangzhou-Shenzhen cooperation lies in the coordinated development of the region driven by the two megacities, and the adjustment of the cooperation policy. The coordination of regional policy systems driven by institutional innovation, the cooperation of major development platforms, and the creation of cooperation structures constitute the core dimension of the Guangzhou-Shenzhen cooperation policy shift, and make the logic of city-region governance based on growth change to integration and coordination. In this process, city-region governance driven by inter-city cooperation is not only a component of the national system, but also a spatial unit of the global system. Intentions of the central government and local development, national security and opening up, urban development, and regional balance all involve the integration and coordination of multiple governance elements and governance processes. The Guangzhou-Shenzhen cooperation has explored a way for the city-region as the basic unit to move towards a coordinated regional development model that pays equal attention to the country and the world.