Probing the dynamic evolution of catalyst structure and chemical state under operating conditions is highly important for investigating the reaction mechanism of catalysis more in depth, which in turn advances the rational design of redox catalysis in using renewable energy to produce fuels. Herein, the evolution of atomically dispersed Cu species supported by mesoporous TiO2 (mTiO2) during the in situ photocatalytic reduction of CO2 with H2O to valuable solar fuels has been reported. The results unveil that the initial atomically dispersed Cu(II) undergoes reduction to Cu(I) and ultimately to Cu(0); the Cu(I)/Cu(0) mixture is proposed to be more effective for CH4 formation. In addition, the enhanced CO2 adsorption ability benefited from the structural advantage of mTiO2 and the elevated charge carrier transfer synergistically contributes to the CO2 photoreduction. It is anticipated that this work would guide the rational design of Cu-based light-harvesting catalysts for artificial CO2 reduction to value-added feedstocks and inspire further interest in using in situ techniques to study the structure-activity interplay of photocatalysts under operating reaction conditions.