Two-dimensional transition-metal oxides have been widely explored as catalysts in high-capacity nonaqueous lithium−oxygen batteries due to their excellent electrochemical performance in the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), but little attention has been paid to non-transition-metal oxides. Here, we employ density functional methods based on the Perdew−Burke−Ernzerhof (PBE) functional with dispersion correction and the Heyd−Scuseria−Ernzerhof hybrid functional (HSE06) to investigate the mechanisms of the nucleation and decomposition processes of Li4O2(s), i.e., discharge and charge processes on single-layer Tl2O (SL-Tl2O) in lithium−oxygen batteries. HSE06 with the spin−orbital coupling effect is adopted to calculate the band gap of SL-Tl2O. It is demonstrated that the spin−orbital coupling effect is significant in predictions of not only electronic but also thermodynamic properties for heavy-element compounds such as Tl2O. The formation of LiO2(s) is initiated by the adsorption of oxygen molecules instead of lithium atoms on the surface. The intermediate reaction products strongly interact with SL-Tl2O, which causes an overpotential of 1.47 V during the electrochemical reaction. The electronic conductivity analysis of lithium oxides adsorbed on SL-Tl2O demonstrates that the electronic conductance of the layer does not change during the ORR/OER. The adsorption enthalpies of five frequently used nonaqueous solvents (tetrahydrofuran, 1,2-dimethoxyethane, 1,3-dioxolane, dimethyl carbonate, and propiolic acid) on SL-Tl2O indicate that SL-Tl2O is stable in the electrolytes. All of these calculated results indicate that SL-Tl2O is a feasible catalyst for the ORR/OER in nonaqueous lithium−oxygen batteries.