Pt/CeO₂ is a typical catalyst for CO oxidation, yet the understanding of its structure–performance relationship and the factors dictating its activity remains to be fully elucidated. In this work, three Pt/CeO₂ catalysts with distinct Pt architectures, namely single atoms (denoted as Pt₁), nanoclusters (~ 1.0 nm, denoted as Pt_CL), and nanoparticles (~ 3.5 nm, denoted as Pt_NP), were investigated using aberration-corrected scanning transmission electron microscopy (STEM), X-ray photoelectron spectroscopy (XPS), X-ray absorption fine structure (XAFS), CO pulse chemisorption, and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The results show that Pt nanoparticles exhibit the lowest oxidation state, the strongest CO adsorption, and the highest turnover frequency (TOF), substantially outperforming Pt clusters and single atoms. According to kinetic analysis, metallic Pt favors a Mars–van Krevelen pathway featuring efficient CO activation and carbonate-mediated turnover. In contrast, isolated Pt²⁺ atoms show weak CO binding and a distinct but less active regime. It is revealed that the metallic state of Pt, rather than dispersion alone, dictates the catalytic activity for CO oxidation on Pt/CeO₂, which offers guidance for designing the next generation of high-performance Pt/CeO₂ catalysts.