The adsorption and dissociation behavior of O₂ molecules on U-Mo alloy surface was studied based on the first-principles simulation. One U atom at the highly symmetrical adsorption sites of the top layer was replaced by one Mo atom, and four U atoms at the top layer were replaced by four Mo atoms, resulting in the fact that γ-U(100)/Mo and γ-U(100)/4Mo slabs were established on the basis of the γ-U(100) slab with five layers. The configuration parameters, adsorption energy, Bader charge, electronic structure, and surface work function were calculated under different adsorption configurations. Results show that the O₂ molecules are chemically absorbed on the γ-U(100)/Mo and γ-U(100)/4Mo surfaces with the adsorption energy of -12.552 and -8.661 eV, respectively. The most stable adsorption configuration is the hollow horizontal adsorption configuration. The O₂ molecule adsorption on U-Mo alloy surface can be divided into dissociated adsorption and undissociated adsorption, which jointly contribute to the stable adsorption behavior. In addition, the dissociated adsorption is more stable than the undissociated adsorption. The Bader charge results show that during the oxygen adsorption, the charge transfer mainly occurs at the atoms of the top two layers of adsorption surface. The electronic structure results show that the slight overlapping hybridization occurs in O 2s with U 6p orbitals. Meanwhile, the strong overlapping hybridization occurs in O 2p with U 6d, Mo 5s, Mo 4p, and Mo 4d orbitals. This research clarifies the O₂ molecule adsorption mechanism on U-Mo alloy surface and provides theoretical basis for the oxidation corrosion mechanism of U-Mo alloy surface.