A rapid helium mass spectrometry leak detection method is established to respond to problems of low sensitivity and efficiency in detecting leaks in large vessels. The optimized multistage tandem leak detection system improves leak detection sensitivity by increasing the amount of gas entering the analysis chamber. By involving the main pumping system in the detection process, the effective pumping speed is increased, resulting in a significant reduction in system response time. Additionally, the optimal leak detection vacuum required for maximizing the leak velocity indicating gas movement is determined, thereby further decreasing the system’s response time. Our application demonstrates that the optimized leak detection system increases sensitivity by one to two orders of magnitude, reduces system response time by over 90%, and shortens evacuation time by 7 h. Ultimately, the optimized design of the vacuum system developed for large vessels demonstrates greatly improved leak detection efficiency and overall capability.