Municipal solid waste incineration and the iron and steel smelting industry can simultaneously discharge NO x and chlorinated organics, particularly polychlorinated dibenzo-pdioxins and polychlorinated dibenzofurans (PCDD/Fs). Synergistic control of these pollutants has been considered among the most cost-effective methods. This work combined experimental and computational methods to investigate the reaction characteristics of a catalytically synergistic approach and gives the first insight into the effect of arsenic (As) on the multipollutant conversion efficiency, synergistic reaction mechanism, and toxic byproduct distribution over a commercial V 2 O 5 −WO 3 /TiO 2 catalyst. The loaded As 2 O 3 species were shown to distinctly decrease the formation energy of an oxygen vacancy at the V−O− V site, which likely contributed to the extensive formation of more toxic polychlorinated byproducts in the synergistic reaction. The As 2 O 5 species strongly attacked neighboring VO sites forming the As−O−V bands. Such an interaction deactivated the deNO x reaction, but led to excessive NO being oxidized into NO 2 that greatly promoted the V 5+ −V 4+ redox cycle and in turn facilitated chlorobenzene (CB) oxidation. Subsequent density functional theory (DFT) calculation further reveals that both the As 2 O 3 and As 2 O 5 loadings can facilitate H 2 O adsorption on the V 2 O 5 −WO 3 /TiO 2 catalyst, leading to competitive adsorption between H 2 O and CB, and thereby deactivate the CB oxidation with water stream.