The aim of this work was to understand the synergistic effect of O2 and H2S on the corrosion behavior of N80 steel in a simulated high-pressure flue gas injection system. Weight loss measurements show that the presence of O2 and an increase in temperature significantly accelerated the general corrosion rate of the N80 steel. We calculated a gray relational grade between different impact factors and the general corrosion rate from the results of an orthogonal experimental corrosion rate. The grade ranking of impact factors was: O2 concentration (0.817) > temperature (0.706) > total pressure (0.689) > H2S concentration (0.665) > CO2 concentration (0.517). Surface characterization of corrosion scales was done using scanning electron microscopy, energy-dispersive spectroscopy, x-ray powder diffraction, and 3D optical microscope analysis. The results show that in the O2-H2S-CO2-H2O coexistence system the products were composed mainly of FeCO3, FeS, Fe2O3, Fe3O4, and elemental sulfur. The results of the corrosion rate test and the characterization show that the presence of O2 greatly accelerated the corrosion process and changed the corrosion mechanism. Elemental sulfur, which was generated by the reaction between the H2S and the O2, participated in the corrosion process of the N80 steel. It could be considered that the synergistic effect of O2 and H2S accelerated the corrosion of the N80 steel. In addition, the porous structures of the corrosion scales and the severe local pits show that the high content of O2 inhibited the formation of FeCO3 and aggravated the corrosion of N80 steel.