Temper embrittlement is a major challenge encountered during the heat treatment of high-performance steels for large forgings. This study investigates the microstructural evolution and mechanical properties of Cr-Ni-Mo-V thick-walled steel, designed for new large forgings with a tensile strength of 1500 MPa, under different tempering cooling rates. Optical microscopy (OM), scanning electron microscopy (SEM), and electron backscatter diffraction (EBSD) were employed to analyze the microstructural features. The results demonstrate that the embrittlement occurring during air cooling after tempering is attributed to the concentration of impurities near Fe3C at the grain boundaries. The low-temperature impact toughness at -40°C after water quenching reaches 29 J due to the accelerated cooling rate during tempering, which slows down the diffusion of impurity elements towards the grain boundaries, resulting in reduced concentration and dislocation density, and increased stability of the grain boundaries, thereby enhancing toughness. the bainite content decreases and the interface between martensite and bainite undergoes changes after water quenching during tempering. These alterations influence the crack propagation direction within the two-phase microstructure, further modifying the toughness. These findings contribute to the understanding of temper embrittlement and provide valuable guidance for optimizing heat treatment processes to enhance the performance of high-performance steels in large forgings.