<p>Metal-support interfaces fundamentally govern the catalytic performance of heterogeneous systems through complex interactions. Here, utilizing operando transmission electron microscopy, we uncover a looping metal-support interaction in NiFe-Fe₃O₄ catalysts during the hydrogen oxidation reaction. At the NiFe-Fe₃O₄ interfaces, lattice oxygens react with NiFe-activated H atoms, gradually sacrificing themselves and resulting in dynamically migrating interfaces. Meanwhile, reduced iron atoms migrate to the {111} surface of Fe₃O₄ support and react with oxygen molecules. Consequently, the hydrogen oxidation reaction separates spatially on a single nanoparticle and is intrinsically coupled with the redox reaction of the Fe₃O₄ support through the dynamic migration of metal-support interfaces. Our work provides previously unidentified mechanistic insight into metal-support interactions and underscores the transformative potential of operando methodologies for studying atomic-scale dynamics.</p>