Selective　methanol　synthesis　via　CO2　hydrogenation　has　been　thoroughly　investigated　over　defective　In-doped　m-ZrO2　using　density　functional　theory　(DFT).　Three　types　of　oxygen　vacancies　(Ovs)　generated　either　at　the　top　layer　(O1_v　and　O4_v)　or　at　the　subsurface　layer　(O2_v)　are　chosen　as　surface　models　due　to　low　Ov　formation　energy.　Surface　morphology　reveals　that　O1_v　has　smaller　oxygen　vacancy　size　than　O4_v.　Compared　with　perfect　In@m-ZrO2,　indium　on　both　O1_v　and　O4_v　is　partially　reduced,　whereas　the　Bader　charge　of　In　on　O2_v　remains　almost　the　same.　Our　calculations　show　that　CO2　is　moderate　in　adsorption　energy　(∼−0.8　eV)　for　all　investigated　surface　models,　which　facilitates　the　formate　pathway　for　both　O1_v　and　O4_v.　O2_v　is　not　directly　involved　in　CO2　methanolization　but　could　readily　transform　into　O1_v　once　CO2/H2　feed　gas　is　introduced.　Based　on　the　results,　the　synthesis　of　methanol　from　CO2　hydrogenation　turns　out　to　exhibit　conspicuous　vacancy　size-dependency　for　both　O1_v　and　O4_v.　The　reaction　mechanism　for　small-sized　O1_v　is　controlled　by　both　the　vacancy　size　effect　and　surface　reducibility　effect.　Thus,　H2COO*　favors　direct　C-O　bond　cleavage　(c-mechanism)　before　further　hydrogenation　to　methanol,　which　is　similar　to　the　defective　In2O3.　The　vacancy　size　effect　is　more　competitive　than　the　surface　reducibility　effect　for　large-sized　O4_v.　Therefore,　H2COO*　prefers　protonation　to　H2COOH　before　C-O　bond　cleavage　(p-mechanism)　which　is　similar　to　the　ZnO-ZrO2　solid　solution.　Furthermore,　we　also　determined　that　stable-CH3O*,　which　is　too　stable　to　be　hydrogenated,　originates　from　the　O1_v　surface.　In　contrast,　CH3O*　with　similar　configuration　is　allowed　to　be　further　converted　to　methanol　on　O4_v.　Overall,　our　findings　offer　a　new　perspective　towards　how　reaction　mechanisms　are　determined　by　the　size　of　oxygen　vacancies.　©　2022　The　Royal　Society　of　Chemistry.