For the complex and changing water transfer conditions along the nullah water transfer project, it is of great significance to analyze the hydraulic response characteristics of the channel pool to ensure the safe and efficient operation of the project. In this paper, using the adjustable reservoir capacity of the channel pool, combined with the earliest and latest regulation time, a method is proposed to determine the optimal regulation time of water conservancy engineering structures through the hydraulic response characteristics. In order to validate the method, the hydraulic response characteristics of the channel pool during the whole regulation period were investigated using an actual river diversion project as an example. By using the Sobol global sensitivity analysis method, the sensitivity analysis of three variables (water transfer flow, upstream initial flow, and downstream water level) was conducted, and the results showed that the change of water transfer flow was the most-critical factor affecting the optimal regulation time. In order to quantitatively study the correlation between the water transfer flow and the optimal regulation time, the water transfer flow factor was coupled to the existing prediction model, and the results showed that the coupled model can efficiently predict the optimal regulation time, and the NSE coefficient can reach 0.98. In addition, the coupled model can be efficiently used to serve on-site dispatchers for accurately predicting the optimal regulation time and making the corresponding safety decisions.