Femtosecond X-ray laser pulses synchronized with an optical laser were employed to investigate the dynamics of the photocatalytic oxidation of CO on the anatase TiO2(101) surface in real-time. Our results provide evidence of ultrafast timescales for the photooxidation of CO to CO2 and clarify the initial mechanism of oxygen activation that is crucial to unraveling the underlying processes for a range of photocatalytic reactions relevant to air purification and self-cleaning surfaces.