Abstract: The preferential oxidation of CO (CO-PROX) reaction is a cost-effective method for eliminating trace amounts of CO from the fuel H₂. Pt-based catalysts have been extensively studied for CO-PROX, with their activity influenced by the morphology of the support. Hydrothermal synthesis was employed to produce different morphologies of γ-Al₂O₃: flower-like γ-Al₂O₃ (f) exposing (110) crystal faces, sheet-like γ-Al₂O₃ (s) revealing (100) crystal faces, and rod-like γ-Al₂O₃ (r) displaying (111) crystal faces, followed by loading PtCo nanoparticles. The exposed crystal faces of the support impact the alloying degree of the PtCo nanoparticles, and an increase in the alloying degree correlates with enhanced catalyst reactivity. Pt₃Co intermetallic compounds were identified on γ-Al₂O₃ (f) exposing (110) crystal faces, and PtCo/γ-Al₂O₃ (f) showed high catalytic activity in the CO-PROX reaction, achieving 100% CO conversion across a broad temperature range of 50−225 °C. In contrast, only partial alloying of PtCo was observed on γ-Al₂O₃(s). Furthermore, no alloying between Pt and Co occurred in PtCo/γ-Al₂O₃ (r), resulting in a reaction rate at 50 °C that was merely 11% of that of PtCo/γ-Al₂O₃ (f). The formation of Pt₃Co intermetallic compounds led to a more oxidized state of Pt, which significantly diminished the adsorption of CO on Pt and augmented the active oxygen species, thereby facilitating the selective oxidation of CO.