Referring to the composition of MA754 alloy, Ni-based alloy powders with high melting point containing Ti and Nb as framework, as well as low melting point Ni-based alloy powders with B and Zr as wetting agents, were prepared by high-energy ball milling. A Ni-based ODS alloy with excellent performance was prepared by spark plasma sintering after mixing two kinds of powder in the optimal ratio. The influence of sintering temperature and the content of low melting point powder in composite powder on the microstructure and mechanical properties of the alloy was studied. The results show that dispersed oxides can be observed in the alloy structure prepared by this method, and the room-temperature strength is improved compared to MA754 alloy, but the plasticity decreases. As the content of low melting point alloy in the composite powder increases, the alloy structure firstly becomes small and uniform, and then acicular aggregate phases and coarse block phases appear. The tensile strength of the alloy shows a trend of firstly increasing and then decreasing. When the sintering temperature is 1025 ℃ and the content of low melting point alloy powder in the composite powder is 3wt%, the alloy has the highest tensile strength of 951.87 MPa, which is significantly improved compared with commercial MA754 alloy. Additionally, the maximum elongation is 11.18%.