The catalytic oxidation of CO at Pt-doped BNNT (5,5) has been investigated theoretically using density functional theory. The electronic structures and thermochemical properties of CO and O2 that adsorbed on Pt embedded at the B- and N-vacancy sites of BNNTs are analyzed. It is demonstrated that the different BNNT substrates canmodify the electronic structure of the Pt catalysts and cause different effects in the catalytic activities. With the Nvacancy (Pt(N)–BNNT), the Pt behaves as a Lewis acid for accepting an electron from the substrate, thus O2 binds stronger than CO molecules, thus alleviating the CO poisoning of the platinum catalysts. Coadsorption of CO and O2 on Pt(N)–BNNT results in additional charge transfer to O2. CO oxidation proceeds via the Eley–Rideal (ER) mechanism entails lower activation barrier and higher reaction rate than that of Langmuir–Hinshelwood (LH) mechanism suggesting the superiority of the ER mechanism for CO oxidation at Pt(N)–BNNT. Therefore, Pt(N)–BNNT might be a good candidate for low-cost, highly active, and stable catalysts for CO oxidation.