Fe2O3 is an attractive catalyst for CO oxidation because of its low cost and reducible nature. Modification in reducible oxide by a noble metal enhances its reducibility. In this work, the effect of noble metal (NM: Pt, Pd) impregnation and substitution on the reaction mechanism for CO oxidation has been studied. Detailed ex situ (X-ray diffraction, XRD; X-ray photoelectron spectroscopy, XPS; and transmission electron microscopy, TEM) and in situ diffuse reflectance infrared fourier transform spectroscopy (DRIFTS) characterization were performed along with kinetic studies to develop mechanistic models. Remarkably, the Fe2O3-supported NM exhibited superior catalytic activity than the NM-substituted Fe2O3. Consequently, XPS, photoluminescence, and DRIFTS studies were performed to understand this behavior. Fe2O3-supported NM showed the formation of metal carbonyl bands in DRIFTS studies, however, carbonates were only observed over Fe2O3-supported Pt. On the basis of the spectroscopic evidence and kinetic studies, the Eley-Rideal mechanism was proposed for pristine Fe2O3, whereas noncompetitive and competitive Langmuir-Hinshelwood mechanisms were proposed for Fe2O3-supported Pt and Pd, respectively. © 2017 American Chemical Society.