Based on the density functional theory (DFT), the reduction properties of Ce_1−xZr_xO₂ (110) surfaces were systematically calculated using CO as a probe for thermodynamic study, and a large supercell was applied to build the whole composition range (x = 0.125, 0.250, 0.375, 0.500, 0.625, 0.750, 0.875). From the calculated energy barriers of CO oxidation by lattice oxygen, we found that composition Ce_0.875Zr_0.125O₂ exhibited the most promising catalytic effectiveness with the lowest activation energy of 0.899 eV. Moreover, the active surface O_3c ions coordinated by two Zr ions and one Ce ion were facilely released from their bulk positions than the O_3c ions surrounded by two Ce ions and one Zr ion on Ce_0.625Zr_0.375O₂, Ce_0.500Zr_0.500O₂, and Ce_0.375Zr_0.625O₂ (110) surfaces. This difference could be explained by the binding strength of O_3c with different neighboring cations.