Electrochemical CO reduction reaction (CORR) offers a promising approach for sustainable acetate production, the promotion of which requires the control of multiple protonation steps. This paper describes the synthesis of atomically isolated Pd sites onto Cu nanoflakes to regulate the protonation of key intermediates. The Pd sites with moderate water activation capability are found to enhance the protonation of *CO at the neighboring Cu site to *COH, which is confirmed to be the rate-determining step through kinetic isotope effect studies. The formation of *COH-*CO is therefore promoted. Additionally, the Pd sites would preferentially protonate the C-OH group in *COH-*CO due to the spatial approximability and electronic modulation effects, generating *CCO for the selective formation of acetate. An acetate Faradaic efficiency of 59.5% is achieved at -0.78 V vs reversible hydrogen electrode (RHE), with a maximum partial current density of 286 mA cm-2 at -0.86 V vs RHE. The optimized catalyst also exhibits long-term stability for 500 h at 100 mA cm-2 in a membrane electrode assembly. This work reveals a new promoting mechanism for selective CORR with simultaneous tuning of the structural and electronic properties of the proton-supplying sites.