The role of vapor- and liquid-phase As2O3 in deactivating commercial V2O5-WO3/TiO2 catalyst during the NH3-selective catalytic reduction (SCR) process was explored and compared. As2O3 was loaded via vapor deposition (As(vap)) and the wet impregnation (As(imp)) method, respectively. Results demonstrated that the poisoning extent of vapor arsenic was much stronger than in the liquid state. Differences in As distribution on the catalyst surface was one of the main causes. Most vapor As2O3 could be oxidized to As2O5, which underwent stacking and formed a dense covering layer on the catalyst surface. In comparison, liquid As2O3 could also be oxidized but distributed uniformly and did not change the catalyst pore structure. Loading arsenic would destroy the V-OH and V=O active sites of the catalyst, and less reactive As5+-OH was generated. Catalyst oxidizability was also enhanced, resulting in NH3 oxidation enhancement, decreased N2 selectivity, and a decline in SCR activity. Importantly, the intermediate of NH3 oxidation, NH2-amide, also could react with NO + O2, and more N2O was generated on the poisoned catalyst during the SCR process, especially on As(imp). Finally, two mechanisms of arsenic poisoning were proposed, in which the role of vapor and liquid As2O3 over the V2O5-WO3/TiO2 catalyst was compared.