Abstract: The empirical method is currently the primary approach for delineating drinking water source protection zones in large reservoirs in China. However, it overly relies on regulatory standards and expert experience, tending toward whole-basin protection. Consequently, it often incorporates non-essential areas into protection zones, restricting regional development. To balance water source safety with development needs, this paper proposes an optimized combined method that integrates MIKE21 numerical simulation with spatial elements, building upon the empirical approach. A large multi-intake reservoir, which integrates water source protection zones, urban development areas, and scenic tourist zones, was selected as a case study to compare and analyze the delineation results of the two methods. The results indicate that the optimized combined method can accurately identify key pollution contribution areas for each intake. While ensuring water quality, it effectively aligns with existing spatial control requirements, such as urban development boundaries and scenic area plans. Following optimization, the total area of the protection zones was reduced by 38.98% compared to the empirical method, with the most significant adjustments observed in the secondary protection zones and quasi-protection zones. This study demonstrates a shift from "whole-basin control" to "precise zoning control," validating the scientific robustness and practical applicability of the optimized combined method. It provides a new pathway for reconciling the conflict between water source protection and regional development.