In this work, Al-Zn-Mg-Cu powders containing 0.15 and 0.33 wt % oxygen were utilized to prepare high-strength aluminum alloys through the process of cold isostatic pressing, sintering, hot extrusion, and heat treatment. Microstructural and mechanical properties at elevated temperatures of 250, 350, and 450 °C were investigated by scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), transmission electron microscopy (TEM), and high-temperature tensile tests. Results showed that the tensile strengths of the obtained Al-Zn-Mg-Cu alloys with 0.15 wt % oxygen were 185, 46, and 18 MPa at 250, 350, and 450 °C, respectively. When the oxygen content of Al-Zn-Mg-Cu alloy rose to 0.33 wt %, the tensile strengths at the corresponding temperature reached up to 205, 68, and 25 MPa, respectively. The excellent high-temperature performance could be attributed to double hindrance to dislocation motion and grain boundary migration by a large amount of nano γ-Al2O3 created by the in-creased oxygen, thereby resulting in fine grains even at high temperatures.