The direct alkoxylation of amides has been accomplished via methoxyiminoacyl (MIA)-mediated Pd-catalyzed C-H functionalization. A diverse array of alkylamide substrates is amenable to this protocol, providing γ-C(sp3)-alkoxylation of alkylamide derivatives with good to high efficiency. Two aspects of the research were completed to explore the reaction mechanism. On the one hand, the result of the kinetic isotopic effect experiment and control experiment indicated that reductive elimination is a rate-limiting step. On the other hand, density functional theory calculations demonstrated that a concerted Sn2 reductive elimination mechanism pathway is prior. Finally, the MIA group could be efficiently hydrogenated and protected in a one-pot procedure, which provides a short synthetic route to γ-methoxy amino acid derivatives.