Segment lining structure is one of the choices to be used for low-to-vacuum maglev tunnels in the future. The airtightness at the joints of the lining structures is one of the critical problems that need to be addressed. However, little attention has been devoted to this problem until now. In this paper, a new apparatus was invented and used to study the mechanical behavior and airtightness sealing capacity of the gasket-in-groove, and a finite element analysis (FEA) model, validated by the test, was developed and used to further investigate thoroughly the sealing performance and sealing failure mechanism of the gasket-in-groove. The results obtained by the above two methods were discussed and compared, and a series of findings were presented. The results showed that the initial pressure distribution on the gasket–gasket contact surface is not uniform due to the presence of the inner holes in the gasket and the grooves between the gasket legs and an approximate “W” shape distribution in this study. The effect of vacuum pressure on the contact pressure distribution is very significant and shows an overall decreasing trend with increasing vacuum pressure. A higher initial maximum contact pressure would provide a better sealing effect but a lower sealing safety factor. Airtightness failure induced by evacuation is a contact surface separation process in which the maximum contact pressure shows a tendency to rise sharply with vacuum pressure increases, followed by a slow drop, and then declines dramatically to zero.