Abstract Urea oxidation reaction (UOR) with a low equilibrium potential offers a promising route to replace the oxygen evolution reaction for energy‐saving hydrogen generation. However, the overpotential of the UOR is still high due to the complicated 6e− transfer process and adsorption/desorption of intermediate products. Herein, utilizing a cation exchange strategy, Ni‐doped CuO nanoarrays grown on 3D Cu foam are synthesized. Notably, Ni‐CuO NAs/CF requires a low potential of 1.366 V versus a reversible hydrogen electrode to drive a current density of 100 mA cm−2, outperforming various benchmark electrocatalysts and maintaining robust stability in alkaline media. Theoretical and experimental studies reveal that Ni as the driving force center can effectively enhance the urea adsorption and stabilize CO*/NH* intermediates toward the UOR. These findings suggest a new direction for constructing nanostructures and modulating electronic structures, ultimately developing promising Cu‐based electrode catalysts.