Ni–10Al-xTa (x = 0, 0.4, 1, 3 wt%) and Ni–10Al-0.4Ta-xY (x = 0.2, 0.4, 0.6 wt%) alloys were prepared by powder metallurgy technology. The effect of Ta and Y on the oxidation resistance mechanism of Ni–10Al alloy at 1100 °C was investigated. The results show that Ta forms Ta-rich regions (including Ni3Ta and Ta oxides) in the alloy matrix. Ta-rich regions on the surface become preferential sites to produce poorly protected NiTa2O6. However, the Ni3Ta in the matrix beneath the oxide film hinders the outward diffusion of Al, reducing the consumption of Al and enhancing the stability of Al2O3 layer. The conflicting effect of Ta allows for a range of Ta additions. The oxidation resistance of Ni–10Al alloy is improved with minor Ta (0.4 wt%) and excess Ta destroys the oxide film. The minor Y addition (0.2 wt%) promotes the adhesion of oxide film, while excessive Y accelerates the production of NiO and the internal oxidation of Al2O3, resulting in an increased oxidation rate. In addition, Y impedes the outward diffusion of Ta, which inhibits the production of NiTa2O6 and Ta oxides in the oxide film.