Copper is well-known to be selective to primary amines via electrocatalytic nitriles hydrogenation. However, the correlation between the local fine structure and catalytic selectivity is still illusive. Herein, we find that residual lattice oxygen in oxide-derived Cu nanowires (OD-Cu NWs) plays vital roles in boosting the acetonitrile electroreduction efficiency. Especially at high current densities of more than 1.0 A cm−2, OD-Cu NWs exhibit relatively high Faradic efficiency. Meanwhile, a series of advanced in situ characterizations and theoretical calculations uncover that oxygen residues, in the form of Cu4-O configuration, act as electron acceptors to confine the free electron flow on the Cu surface, consequently improving the kinetics of nitriles hydrogenation catalysis. This work could provide new opportunities to further improve the hydrogenation performance of nitriles and beyond, by employing lattice oxygen-mediated electron tuning engineering.