The influence of vapor and SO2 in coal firing flue gas on the selective catalytic reduction activity of Mn/γ-Al2O3 and Mn–Fe/γ-Al2O3 catalysts was investigated at 150–275 °C. Denitration experiments and detailed characterization of catalysts were conducted. Vapor had no chemical effects on denitration, and the mechanism of SO2 deactivating the Mn/γ-Al2O3 catalysts was investigated in detail. This is due to the reaction between MnO2 and SO2 and the ammonium sulfate deposits forming on the surface. Sulfation of the Mn-active component was significantly reduced by doping the Mn/γ-Al2O3 catalyst with Fe. Iron doping also lowered the stability of the ammonium sulfate surface deposits, forcing them to rapidly decompose. Thus, iron doping significantly improved SO2 resistance and the denitration efficiency of Mn–Fe/γ-Al2O3 catalysts was not clearly decreased.