Formulating knowledge of structure-function relationships in heterogeneous catalysis is central to the design of efficient catalysts; yet, the elucidation of dominant reaction sites has remained as a challenge. Here, we present a methodology that can be used to visualize metal-gas and metal-oxide-gas interfaces in three dimensions and to quantify their catalytic activity levels. As a case study, CH4 oxidation occurring in a Pt/CeO2 system is chosen. By employing thermally robust Pt@CeO2 model catalysts with size-tunable and monodisperse cores, and gas-permeable shells, we reconstruct a series of structures in 3D via electron tomography and match the information to activity data and theoretical calculations. This strategy reveals that two different interfaces catalyze the CH4 oxidation and that their contribution to the overall rate changes with the Pt size, temperature, and gas atmosphere. Our results provide an analytic platform on which to explore reaction pathways and mechanisms applicable to multiple reactions and materials.