An iterative electrochemical activation process is demonstrated to maximize the interface between Ag and CuxO. Morphological reconstruction and phase transformation of CuxO occurs through the iterative electrochemical redox reaction, as indicated by energy-dispersive spectroscopy and X-ray photoelectron spectroscopy. The activated Ag/CuxO/C catalysts exhibits enhanced oxygen reduction reaction performance, with an onset potential of 0.86 V vs. the reversible hydrogen electrode, a Tafel slope of 46 mV dec(-1), and a high stability as compared to Ag/C. A mechanistic study using density functional theory shows that the weakened binding energy of the OH intermediate, originating from the charge transfer from Ag to CuxO, improves the ORR activity at the interface sites of the Ag/CuxO electrocatalysts. Ag/CuxO shows a higher limiting potential of 0.14 V for interface sites than isolated Ag nanoparticles. The interfacial charge transfer between Ag and CuO is verified experimentally.