CO poisoning is a major problem for Pt-based catalysts in various catalytic processes. Thus, the prediction of CO binding energies over Pt alloy surfaces is fundamentally important to evaluate their CO poisoning tolerance. This article describes the effect of surface and subsurface coordination environments on the CO binding strength over PtCu alloy surfaces by employing density functional theory calculations. We show that the existence of surface Pt neighbors weakens the CO binding strength on Pt, whereas the subsurface Pt neighbors play the opposite role. Crystal orbital Hamilton population analysis suggests a stronger antibonding interaction for the Pt-surface -Pt-subsurface bond than for the Pt-surface -Pt-surface bond, which indicates less stable subsurface Pt atoms that hence generate an activated surface Pt that attracts CO more strongly. On the basis of the calculated CO binding energies, an empirical formula, with Pt-Pt coordination numbers as the variables, has been fitted to achieve a fast prediction of CO binding energy over PtCu alloy surfaces.