Surface engineering of transition metal layered double hydroxides (LDHs) provides an efficient way of enhancing their catalytic activity toward the oxygen evolution reaction (OER). However, the underlying mechanism of atomistic doping or heterogeneous interface with foreign atom is still ambiguous. Herein, a case study of NiFe‐LDHs that are homogeneously doped with Ce (CeNiFe‐LDH) and interfaced with Ce(OH)3 (Ce@NiFe‐LDH), which elucidates their electronic modulation, in situ evolution of active site, and catalytic reaction mechanisms by using X‐ray photoelectronic spectroscopy, operando electrochemical Raman spectroscopy, and first‐principles density functional theory (DFT) calculations, is reported. The results indicate that Ce and Fe atoms serve as the electron acceptors and facilitate the coupled oxidation of Ni3+/4+ in NiFe‐LDH, and the activated oxyhydroxide phase of the catalysts exhibits superior catalytic activity for water oxidation. Especially, Ce@NiFe‐LDH shows a stronger electron transfer between the loaded Ce(OH)3 and the matrix, which leads to a better catalytic activity than CeNiFe‐LDH. DFT calculations provide a clear picture with atomistic resolution for charge redistribution in the NiFe‐LDH surface induced by Ce, which eventually leads to the optimal free energy landscape for the enhanced OER catalytic activity. Two NiFe‐layered double hydroxides (LDHs) doped with Ce (CeNiFe‐LDH) and interfaced with Ce(OH)3 (Ce@NiFe‐LDH) are studied to reveal the enhancement mechanism of water oxidation. In the Ce‐modified NiFe‐LDHs, Ce and Fe atoms serve as the electron acceptors and facilitate the coupled oxidation of Ni3+/4+ in NiFe‐LDH. Dissimilar charge redistribution in CeNiFe‐LDH and Ce@NiFe‐LDH is revealed, which accounts for superior catalytic activity for water oxidation.