It has been widely accepted that oxygen vacancies are critical to catalytic oxidation activities. However, the effects of Ce–O bond strength on the formation of oxygen vacancies and the oxidation rate of styrene remain ambiguous. Herein, a series of CeO2 (CeO2-100, CeO2-140, CeO2-180) were synthesized to uncover the effects of Ce–O bond strength on surface chemical properties and unravel the oxidation mechanism of styrene via comprehensive characterization techniques and theoretical calculations. DFT calculations showed a positive correlation between the Ce–O bond strength and the formation of oxygen vacancies. The CeO2-100 catalyst exhibited a lower styrene degradation temperature (T100 = 223 °C) and the lowest apparent activation energy (Ea = 19.12 kJ/mol). This is due to the fact that weakening the Ce–O bond strength would make it easier to generate oxygen vacancies. More oxygen vacancies facilitate the adsorption of styrene and the formation of surface adsorbed oxygen, thereby accelerating styrene oxidation. In situ DRIFTS demonstrated that more oxygen vacancies can accelerate the oxidation of important intermediate products and further promote the deep oxidation of styrene to CO2 and H2O. Furthermore, the CeO2-100 catalyst showed better activity stability at 223 °C and good water resistance in the presence of 10 vol % water.