[Objective] This study aims to select appropriate evaluation methods to comprehensively quantify the economic benefits of the Middle Route of South-to-North Water Diversion Project in Henan Province, and provide reference for the construction of a sound comprehensive benefit evaluation index system and the refinement of evaluation methods. [Methods] The evaluation is structured vertically into two phases: the construction phase and the operational phase, aligned with the project’s lifecycle. Horizontally, it distinguishes between macroeconomic benefits and direct water supply benefits. Using 2014 as the base year and 2023 as the evaluation year, the assessment covers macroeconomic benefits including the economic stimulus from construction investments and the macroeconomic support from water supply during operation. Direct water supply benefits encompass urban water supply and irrigation benefits. Methodologies employed include statistical analysis, investment multiplier, and water supply benefit allocation coefficient methods. [Results] The Middle Route of South-to-North Water Diversion Project in Henan Province has generated 150.2 billion yuan in investment-driven benefits during its construction phase, with operational water supply providing 5.493 534 trillion yuan in economic support. In terms of direct water supply benefits, urban areas receiving water from the Middle Route in Henan have achieved cumulative economic returns of 147.704 billion yuan, while irrigation water supply has contributed 16.235 billion yuan in cost-sharing benefits. [Conclusions] The Middle Route of South-North Water Diversion Project has brought significant economic benefits to Henan Province. The factors influencing the cost-sharing coefficient for urban and irrigation water supply are numerous, and further detailed research is recommended for the next phase.