A series of Na-OMS-2 catalysts was prepared by a facile solid-state reaction method. Their physiochemical properties were characterized, and the catalytic activity for ozone decomposition was evaluated. The results showed that the introduction of Na+ in the tunnel framework of OMS-2 facilitated lattice defect formation, which significantly enhanced oxygen vacancies, which are believed to be the active sites for ozone decomposition. Density functional theory calculations also showed that both the oxygen vacancy formation energy and ozone adsorption energy over Na-OMS-2 decreased because of Na+ introduction. Sodium ion introduction significantly improved the OMS-2 catalytic activity for ozone decomposition. The Na-OMS-2 catalyst with a Na/Mn molar ratio of 1/4 exhibited ozone conversion at 92.5% at 25 ± 1 °C after reaction for 6 h under an initial ozone concentration of 45 ± 2 ppm, a relative humidity of 30 ± 2%, and a space velocity of 660 000 h-1. This showed that this catalyst was far superior to manganese oxide catalysts reported to date. Furthermore, the research results also showed that the catalytic activity of Na-OMS-2 deactivated by the accumulation of oxygen-related intermediates was recovered by calcination at 425 °C under N2 atmosphere for 0.5 h. Finally, a complete mechanism for ozone decomposition, catalyst deactivation, and regeneration was proposed.