Taking CO oxidation as a probe, we investigated the electronic structure and reactivity of Pt atoms stabilized by vacancy defects on hexagonal boron nitride (h-BN) by first-principles-based calculations. As a joint effect of the high reactivity of both a single Pt atom and a boron vacancy defect (PtBV), the Pt–N interaction is −4.40 eV and is already strong enough to prohibit the diffusion and aggregation of the stabilized Pt atom. Facilitated by the upshifted Pt-d states originated from the Pt–N interaction, the barriers for CO oxidation through the Langmuir–Hinshelwood mechanism for formation and dissociation of peroxide-like intermediate and the regeneration are as low as 0.38, 0.10 and 0.04 eV, respectively, suggesting the superiority of PtBV as a catalyst for low temperature CO oxidation.