A technique widely used to mitigate climate change is the minimization of energy consumption in buildings by enhancing the thermal performance of glazing systems. Rim seals, consisting of a primary seal, secondary seal, and spacer, are the key to securing a good thermal performance because they protect the gaseous cavities of the multi-pane glazing systems, thus providing a long service life and good appearance. Fatigue due to wind pressure is a major aging factor for rim seals, and it deteriorates their moisture barrier performance. This study estimates the wind-inducing deflection of a 2-m-high double glazing system considering the wind strength and frequency of wind occurrence. A fatigue load was repeatedly applied to estimate the deflection movements in the rim seals. The results show that the repeated movements, which can be regarded as the accumulated fatigue damage over 25–50 years, increase the moisture permeability of the rim seals. A rim seal therefore can potentially lose its moisture barrier property with time. Our experimental results also provide a solution for reducing the change in the moisture permeability of the rim seals. A rim seal can exhibit stable moisture permeability after a fatigue test, when the boundary between the primary and secondary seals is not adhered. The lateral sides of the primary/secondary seals adjacent to the non-adhered boundary can move more freely (especially in a tensile condition) and independently than those adjacent to an adhered boundary and consequently may experience lower stresses. It is also important to design the section dimensions accurately. Thus, this study proposes a fundamental mechanism for maintaining a good moisture barrier property in rim seals. Further research is needed to investigate the stress distribution in different boundary conditions and the impact of other aging factors, such as heat and ultraviolet radiation.