The design of efficient catalysts with great water-resistance for volatile organic compounds (VOCs) degradation is challenging. Herein, series of Mn-based catalysts with great catalytic activity were prepared via a novel non-thermal derivation by Na2CO3 solution treatment using Mn-MIL-100 as a sacrificial template. Among them, the Mn-Na-1.0 catalyst prepared by treating with 1.0 mol/L Na2CO3 solution presented the optimal toluene degradation performance (T90 = 209 °C) and water-resistance (5.0 vol%). Characterization results suggested that the abundant surface Mn3+ and Oads species, better surface lattice oxygen species mobility, low-temperature reducibility, and high surface area accounted for the great catalytic performance of the Mn-Na-1.0 catalyst. Importantly, the promotion of water vapor to toluene oxidation was observed and systematically elucidated by many characterizations and experiments. The results showed that the introduced water vapor was activated and dissociated to form dissociation adsorbed active oxygen species, which served as the additional active site and provided active oxygen species to accelerate the oxidation of intermediates and toluene mineralization. This work provided a novel approach for designing Mn-based catalysts with good water-resistance in VOCs degradation under actual industrial conditions.