The search for efficient non-noble-metal catalysts able to perform selective oxidation reactions is of great importance, with relevance to many catalytic processes. However, this is often hampered because the origin of the selectivity remains controversial, particularly for reactions catalyzed by oxides. Here, combining high-pressure surface imaging techniques and theoretical calculations, we identify that spatially separated active sites for O2 activation and H2 adsorption on an ultrathin Mn3O4 surface enable selective oxidation of CO over H2. Theoretical calculations reveal that Mn-O pairs for H2 dissociation are separated from Mn-Mn pairs for the formation of adsorbed O2* so that H2 has to surmount much higher barriers for both H2 dissociation and H diffusion while CO can directly react with O2* following the Eley-Rideal process. Our study sheds light on the atomic-level understanding of the surface structure-dependent selective oxidation reaction on oxide catalysts.