The river diversion project from the Yangtze River to the Hanjiang River serves as a supplementary water source for the Middle Route of the South-to-North Water Diversion Project. To ensure water quality safety in the middle and lower reaches of the Hanjiang River and to safeguard urban and rural water supplies in Hubei Province, it is essential to delineate a drinking water source protection area around the project’s water intake. In comprehensive considerations on water quality protection requirements, transportation and shipping, port construction and development, as well as emergency response needs, this study designs scenarios for various operational conditions, including different water levels of the Three Gorges Dam, representative flow rates for engineering diversion, and corresponding water quality conditions. It integrates hydrodynamic and water quality model simulations with emergency response time analysis to define and recommend the drinking water source protection zone for the Longtan Creek intake. The results suggest that the protection zone radius around the Longtan Creek intake should be no less than 1.3 kilometers. This recommendation provides technical support for the future delineation of protection areas.