Aldehyde　deformylations　occurring　in　organisms　are　catalyzed　by　metalloenzymes　through　metal-dioxygen　active　cores,　attracting　great　interest　to　study　small-molecule　metal-dioxygen　complexes　for　understanding　relevant　biological　processes　and　developing　biomimetic　catalysts　for　aerobic　transformations.　As　the　known　deformylation　mechanisms,　including　nucleophilic　attack,　aldehyde　α-H-atom　abstraction,　and　aldehyde　hydrogen　atom　abstraction,　undergo　outer-sphere　pathways,　we　herein　report　a　distinct　inner-sphere　mechanism　based　on　density　functional　theory　(DFT)　mechanistic　studies　of　aldehyde　deformylations　with　a　copper　(II)-superoxo　complex.　The　inner-sphere　mechanism　proceeds　via　a　sequence　mainly　including　aldehyde　end-on　coordination,　homolytic　aldehyde　C-C　bond　cleavage,　and　dioxygen　O-O　bond　cleavage,　among　which　the　C-C　bond　cleavage　is　the　rate-determining　step　with　a　barrier　substantially　lower　than　those　of　outer-sphere　pathways.　The　aldehyde　C-C　bond　cleavage,　enabled　through　the　activation　of　the　dioxygen　ligand　radical　in　a　second-order　nucleophilic　substitution　(SN2)-like　fashion,　leads　to　an　alkyl　radical　and　facilitates　the　subsequent　dioxygen　O-O　bond　cleavage.　Furthermore,　we　deduced　the　rules　for　the　reactions　of　metal-dioxygen　complexes　with　aldehydes　and　nitriles　via　the　inner-sphere　mechanism.　Expectedly,　our　proposed　inner-sphere　mechanisms　and　the　reaction　rules　offer　another　perspective　to　understand　relevant　biological　processes　involving　metal-dioxygen　cores　and　to　discover　metal-dioxygen　catalysts　for　aerobic　transformations.　©　2022　American　Chemical　Society.　All　rights　reserved.