This paper presents a two-dimensional computational fluid dynamics (CFD) study to investigate the performance of our high-throughput fixed-bed reactor used for the total oxidation of diluted volatile organic compounds (VOCs) in a continuous gas stream. The CFD model, based on a porous medium and a power-law kinetic model, is validated by comparing the calculated and experimentally determined conversion of methane, the selected VOC, over the β-cyclodextrin-Cu/hydroxyapatite catalyst for different operating conditions. The CFD model captures the effect of varying partial pressures of methane and oxygen on the methane conversion at various space times and temperatures. Overall, the simulation results qualitatively agree with experimental data within an average deviation of 17%. Analysis of the flow field, calculated using CFD, suggests that the reactor behavior resembles that of an ideal plug-flow reactor. The findings set out the lines for creating a simplified one-dimensional model of the high-throughput reactor in future research.