In this study, Ti-48Al-3Nb-1.5Ta powders were manufactured from cast bars by the supreme-speed plasma rotating electrode process (SS-PREP) and used to prepare hot isostatically pressed (HIPed) material at 1050–1260 °C with 150 MPa for 4 h. The phase, microstructure and mechanical performance were analyzed by XRD, SEM, electrical universal material testing machine and other methods. The results revealed that the phase constitution changed from γ phase to α2 phase and then to γ phase with the material changing from as-cast to powders and then to as-HIPed. Compared with the as-cast material, the grain size and element segregation were significantly reduced for both powders and as-HIPed. When the hot isostatic pressing (HIP) temperature was low, the genetic characteristics of the powder microstructure were evident. With the HIP temperature increasing, the homogeneity of the composition and microstructure increased, and the prior particle boundaries (PPBs) gradually disappeared. The elastic moduli of powder and as-HIPed were superior to those of as-cast, which increased with the HIP temperature increasing. The hardness of as-HIPed was lower than that of the powder. The compressive strength, compressive strain, bending strength, and tensile strength of as-HIPed were higher than those of as-cast. With an increase in the HIP temperature, the compressive strength decreased gradually, and the compressive strain first decreased and then increased.