An intact oxide scale adhering well to the matrix is crucial for the safe service of metallic materials at high temperatures. However, premature failure is usually caused by spallation of scales from the matrix. Although few mechanisms have been proposed to understand this phenomenon, consensus has not yet been reached. In this study, we reveal that trace sulfur impurities contaminated in high-purity raw materials prominently segregate to the interface and form a thin intermediate amorphous-like layer between the oxide scale and alloy matrix during the oxidation process. Subsequently, cracking and spallation occur preferentially between the sulfur-rich layer and alumina scale due to the weak bonding between sulfur and alumina atoms. We validate the revealed atomistic spalling mechanism by successfully eliminating the detrimental effect of sulfur via microalloying. Our findings are useful for improving adhesion of oxide scales and enhancing heat-resistant properties of other high-temperature alloys.