Phenol wet oxidation over deactivating catalysts in three-phase moving-bed reactors was simulated by formulating and solving a two-scale, nonisothermal, non-steady-state model to highlight the strength of on-stream catalyst replacement, in comparison to catalyst-batch fixed-bed reactors. Simulation results indicate that three-phase moving-bed reactors offer a promising alternative to fixed-bed reactors. The autonomy of fixed-bed reactors is limited due to severe reduction of catalyst activity, while in moving-bed reactor configurations, the decline of pollutant conversion is reduced with increased solid velocity, to compensate for the decrease in catalyst activity loss. The fixed-bed reactor operates in non-steady-state mode, because of the continuous decline of catalyst activity while moving-bed reactors evolve to steady-state operation after a transient period. Decreasing the reactor feed phenol concentration and increasing liquid residence time in the reactor and feed temperature are the best ways to oppose rapid deactivation of catalyst in moving-bed reactors.