This study investigates the effect of heat treatment temperature on the intergranular oxidation behavior of 45# structural steel under simulated hot-rolling furnace atmospheric conditions (17% CO2, 32% N2, 34% CO, and 17% H2). Experiments were conducted across a temperature range of 500–1250 °C, with oxidation depth and morphology analyzed using metallographic and energy-dispersive spectroscopy (EDS) techniques. The results show that intergranular oxidation in 45# steel initiated at 800 °C, forming hairline-like oxides along grain boundaries, with no significant oxidation below 750 °C. EDS analysis revealed selective enrichment of silicon (≤3.2%) and manganese (≤2.5%) at grain boundaries, while intragranular regions remained minimally affected. Oxidation depth increased from 11.20 μm (900 °C) to 74.37 μm (1250 °C), exhibiting the most rapid growth between 1000 and 1150 °C before plateauing at higher temperatures. Morphologically, oxides transitioned from grain-boundary networks (800–950 °C) to dispersed dots (≥1000 °C), driven by dominant lateral oxygen diffusion at elevated temperatures. These findings provide critical insights for optimizing heat treatment parameters to mitigate oxidation-related defects in hot-rolled products. The results highlight the critical role of temperature in controlling intergranular oxidation, providing a theoretical basis for optimizing slab reheating parameters to mitigate surface defects in hot-rolled products. Practical implications include reducing scrap rates and enhancing surface quality for high-end applications.