In this work, elevated temperatures in vacuum is reported to be capable of enhancing the endurability of injection molded isotactic polypropylene (iPP) against photo-oxidation. Annealing in vacuum gives rise to higher crystallinity due to newly formed crystals and lamellae thickening and perfection together with the formation of looser amorphous phase, the declining mechanical coupling between crystalline and amorphous phase and occurrence of orientation relaxation. A synergistic mechanism is proposed to explain the enhanced aging resistance of iPP with elevated annealing temperature, including the decreased solubility coefficient of oxygen, the improved radical scavenging ability of crystals, the inhibited chain scission in interfacial regions and amorphous phase. Our work suggests that high-temperature annealing in vacuum is not only an effective strategy in manipulating the multi-level aggregation structure of semicrystalline polymers, but also may serve as an effective and promising method to enhance the resistance of polymers such as iPP against photo-oxidative degradation.