The changing airtightness of a High-Speed Train (HST) in its life cycle may bring riding discomfort and safety issues. For studying the issue, on-board field tests were carried out on a series of in-service trains. Combining the measured internal pressure with one-dimensionally calculated exterior pressure wave and vehicle status information, the actual airtight performance was cross-compared and analyzed. The results showed the airtightness was in a non-monotonic trend along an increasing total operating mileage, which indicated different grades of overhaul greatly affected a HST’s airtight performance. After an overhaul, the airtight performance showed a deteriorating law in power function with exponent 0.2 quantified by the local pressure change peaks, which could be mainly determined by a leakage increase on the train body. Due to the different airtight-related contents, the restoring effect of Lv3 and Lv4 accounts for 9% and 43% to a Lv5 overhaul. Through considering the overhaul grades and the deteriorating law, a new quantifying concept ‘effective mileage’ was proposed to estimate the airtightness of a HST in any phase. It is verified as practical and can well sequence the evolution of the airtight performance. This paper provides a significant reference for understanding the airtightness in a HST’s life cycle.