A method to assess the impact of deactivation phenomena on the global performance of a catalytic reactor was developed. The methodology is applied here to the case of CO methanation, where the catalyst is subject to deactivation by coking. This method can be extended to other reactions and deactivation mechanisms. The method is based on the integration of a single differential equation to describe the activity of the catalyst and on the evaluation of the profiles in the reactor through consecutive steady states at progressively lower activity values. The model was applied successfully to both fixed- and fluidized-bed methanation, with small differences between the two cases. This model showed promising results in a case study, with a correct description of the decrease in the level of CO conversion due to coking. It also allowed us to observe the higher resistance to deactivation of fluidized-bed reactors compared to fixed-bed ones at similar conditions. The time needed to reach 25% conversion in fluidized-bed reactors was calculated to be 5 to 50 times higher compared to that in fixed-bed reactors. The model allows optimizing the reactor with respect to deactivation, acting on the reactor geometry, size, and operating conditions to achieve the best long-term performance.