First-principles calculations were performed to investigate the catalytic activity of Ti2C MXene material as a potential cathode in Li–O2 batteries. Stable non-, O-, F-, OH-terminated Ti2C MXenes are constructed to show the real state of Ti2C MXene monolayer in the experiment. Then, the interfacial models of LixO2 (x = 4, 2, and 1) molecules adsorbed on Ti2C, Ti2CO2, Ti2CF2, and Ti2C(OH)2 MXenes were used to simulate the structural evolution during discharging (oxygen reduction reaction, ORR) and charging (oxygen evolution reaction, OER) processes. The catalytic activity was quantitatively assessed by calculating the ORR and OER overpotentials. Among them, Ti2CO2 MXene displays the best catalytic activity with the lowest ORR/OER/TOT overpotential, suggesting that O-terminated Ti2C MXene is more favorable for Li–O2 batteries. This is because the Ti 3d orbital of the Ti2CO2 surface is completely polarized near the Fermi level, showing strong oxidation capability toward O22–. These findings give a theoretical guidance for Ti2C MXene used in Li–O2 batteries and widen the applications of MXene-based materials.