The effect of the active element yttrium and its content on the oxidation behavior of GH4169 Ni-based superalloy at extreme temperature was studied by isothermal oxidation experiments. The results show that the oxide scale of GH4169 alloy presents a multi-layer structure, in which the continuous and dense Cr2O3 oxide layer is located in the subouter layer (II layer) and the continuous Nb-rich layer is in the subinner layer (III layer). These layers can inhibit the diffusion of oxygen and alloying elements, preventing the further oxidation of the alloy. The appropriate addition of yttrium can promote the selective oxidation of Cr element, reduce the thickness of the oxide scale and the oxidation rate of the alloy, inhibit the formation of voids at the interface of the oxide scale/alloy matrix, improve the resistance of the alloy to spalling as well as the adhesion of the oxide scale, and improve the high-temperature oxidation resistance of the alloy. Of those tested, the alloy containing 0.04 wt.%Y has the lowest oxidation weight gain, the slowest oxidation rate, and less oxide scale spalling. Based on this, the effect of yttrium on the high-temperature oxidation behavior of GH4169 Ni-based superalloy and its mechanism were revealed.