[Objective] The water source area of the Middle Route of the South-to-North Water Diversion Project faces issues such as water quality safety risks, dual challenges in scheduling, and a lack of coordinated monitoring due to fragmented and decentralized management. This study aims to construct a holistic collaborative management mechanism for the water source area and to provide a reference for the “four unifications” management practice, thereby ensuring the high-quality development of the Hanjiang River Basin and the achievement of the goal of “a continuous flow of clean water going northward forever”. [Methods] Based on the theoretical foundation of holistic governance theory and the classic SFIC collaborative management analysis model, the study systematically drew on the collaborative management experiences of the Murray-Darling River and the North American Great Lakes. By analyzing 232 policy documents and 21 relevant important speeches, nine key elements were extracted and summarized into three dimensions: collaborative bodies, basin-wide coordination, and support and safeguard. Finally, the holistic collaborative management mechanism for the water source area was constructed. [Results] The study constructed a five-dimensional holistic collaborative management mechanism model for the water source area of the Middle Route Project of South-to-North Water Diversion Project, consisting of “initial conditions - catalytic leadership - institution design - collaboration process - outcome assessment”. Initial conditions focused on enhancing the motivation for collaboration among multiple bodies. Catalytic leadership coordinated and integrated efforts by improving communication and coordination mechanisms. Institutional design ensured the fairness and legality of collaboration through the establishment of a comprehensive legal system. The collaboration process created a virtuous cycle of cooperation among multiple bodies. Outcome assessment continuously optimized collaborative results. Based on this model, five policy recommendations were proposed: establishing a unified management institution for the water source area, unlocking market potential to promote overall synergy, improving coordination and compensation mechanisms, ensuring the sufficiency and stability of various resources, and perfecting the legal and regulatory system of the water source area. Research on holistic collaborative management not only enriched the theory of system governance but also provided practical guidance for the management of water source areas in water diversion projects, serving as an effective reference for the transition from local to holistic collaboration. [Conclusion] This study overcomes the limitation of previous research on water source area collaborative management that focused primarily on local collaboration, concentrating instead on the holistic collaborative management of the water source area of the Middle Route Project of South-to-North Water Diversion Project. Based on the theoretical foundation of holistic governance theory and the SFIC model, and drawing on the collaborative management experiences of the Murray-Darling River Basin and the North American Great Lakes, the study analyzes laws, regulations, policies, and key speeches from a holistic collaborative management perspective, distills the key elements of holistic collaborative management, and then constructs the holistic collaborative management mechanism for the water source area. Five targeted policy recommendations were proposed. The study provides a reference for addressing the challenges of fragmented and decentralized management in the water source area, and is of great significance for ensuring the smooth operation of the Middle Route Project, supporting the construction of the national water network, and promoting the synergistic development of ecology, livelihood, and economy along the route.