Catalytic oxidation of propane as a representative molecule of light hydrocarbons (LHs) is of special interest for energy utilization and pollution abatement but is challengeable due to its stable C–H bonds. Here, Ru supported on porous and defect-rich CeO₂ nanosheets catalysts were prepared and investigated for catalytic oxidation of propane, and the Ru/CeO₂ catalyst using chlorine-free Ru precursor (RuN/CeNS) presented an ultra-high activity with complete conversion at 150 °C. A series of well-designed experiments and characterizations illustrated that the high-density and uniform Ru-O-Ce interfaces were determinant for propane oxidation due to the possible asymmetric bridged adsorption and activation. The presence of chlorine species suppressed the dispersion of RuO_x species and the formation of Ru-O-Ce interfaces, which also accelerated the sintering of CeO₂ and Ru-O-Ce interfaces at high temperatures. This work highlighted the experimental insights into the active interfacial sites of ultra-active Ru/CeO₂ for propane oxidation. It contributed to an in-depth understanding of the activation of C–H bonds in LHs and the preparation of supported noble metal catalysts.