The Pd-Ce-Zr solid solution catalysts were in situ synthesized by a sol-evaporation induced self-assembly (SEISA) method. The catalytic performances of the as-prepared catalysts for CO oxidation and their physicochemical properties were investigated with various characterization techniques. The catalysts with low doping amount of Pd exhibited unique thermal stability and high activity toward CO oxidation. The CO oxidation activities of the catalysts showed a volcano type relationship with the content of Pd doping in Ce-Zr oxides. Pd-Ce(0.8)Zr(0.2)O2 with 1.0% Pd doping gave the highest catalytic activity. Its CO complete conversion temperature was 110 °C with a turnover frequency of 1.52 s(-1). Density functional theory (DFT) calculations suggested strong effects of Pd doping on the crystal structure, charge distribution and formation of oxygen vacancy of the Ce-based catalysts. The calculations also suggested that CO oxidation on Pd doped Ce-based catalysts follows Eley-Rideal mechanism, and the direct reaction of CO with a surface oxygen atom appears to be the main pathway of the oxidation.