The CO methanation reaction, which achieves the carbon cycle and gains value-added chemicals, has attracted much attention, but the design and exploitation of highly active catalysts remain a big challenge. Herein, zirconium dioxide-supported Ni catalysts toward low-temperature CO methanation are obtained via structural topological transformation of NiZrAl-layered double hydroxide (LDH) precursors, which have the feature of an interfacial structure (Ni-O-Zr-Vö) between Ni nanoparticles and ZrO support (0 < < 1). The optimized catalyst (Ni/ZrO-S2) exhibits exceptional CO conversion (∼72%) at a temperature as low as 230 °C with a ∼100% selectivity to CH, without obvious catalyst deactivation within a 110 h reaction at a high gas hourly space velocity of 30,000 mL·g·h. Markedly, the space-time yield of CH reaches up to ∼0.17 ·g·h, which is superior to previously reported Ni catalysts evaluated under similar reaction conditions. Both in situ/operando investigations (diffuse reflectance infrared Fourier transform spectroscopy and X-ray absorption fine structure) and catalytic evaluations substantiate the interfacial synergistic catalysis at the Ni/ZrO interface: the Zr-Vö facilitates the activation adsorption of CO, while the H molecule experiences dissociation at the metallic Ni sites. This work demonstrates that the metal-support interface effect plays a key role in improving the catalytic behavior toward CO methanation, which can be extended to other high-performance heterogeneous catalysts toward structure-sensitive systems.