Lithium-carbon dioxide (Li-CO2) batteries are considered as a most auspicious energy storage systems owing to their high capacity and the ability of capturing CO2. However, there are still some critical issues needed to be addressed before their practical application, such as high charge potential and poor cyclability. Herein, oxygen vacancy-enriched TiO2 nanoparticles grown in situ on Ti3C2Tx MXene (OV-TiO2/MXene) are synthesized as catalysts for Li-CO2 batteries by facile one-step ethanol heat treatment of the MXene nanosheets. The thermodynamically metastable Ti atom on the surface of MXenes serves as nucleating sites, which play a critical role in generating the relatively stable vacancy-rich TiO2 nanoparticles. The spontaneously generated oxygen vacancies can enhance CO2 adsorption, which is beneficial to CO2 involved electrode reactions. The Li-CO2 batteries with OV-TiO2/MXene electrodes deliver noteworthily reduced charge voltage of 3.37 V at 100 mA g−1, and a superb cycling performance of 158 cycles. This work highlights the significant role of oxygen vacancies in activating CO2 in Li-CO2 batteries, instrumental to the development of high-performance electrocatalysts for Li-CO2 batteries and beyond.