Water–air interaction (mixing of gas and water and gas dissolution into water) is one of the main reasons for gas loss in air cushion surge chambers. With the increase of water head in hydraulic power generation systems, the heat and mass transfer process at the water–air interface under high-pressure conditions intensifies, and the water–air interaction is further strengthened. If some gas is mixed/dissolved in water and enters downstream pipelines, it will affect the safety of the unit. At present, there has been no theoretical or systematic research on gas loss and related water gas two-phase flow in air cushion surge chambers under high-pressure conditions. Therefore, this article established an air loss model for an air cushion surge chamber based on the VOF model and gas–liquid mass transfer theory. We analyzed the mechanism of gas loss in the gas chamber through simulation and quantitatively expressed the gas loss. The results indicate that during a typical large fluctuation process, the gas–liquid mass transfer process at the water–air interface, air mass, and vortex is very strong, with a pressure chamber of approximately 923.89 m3. The gas dissolved in water enters the water diversion system, with a length of 28.75 m3. High pressure gas enters the water diversion system in the form of air masses. When considering the water inlet on the right side of the air chamber, the total gas loss in the air chamber is slightly lower (854.18 m3) and no mixed air mass was detected entering the connecting pipe.