Producing hydrogen peroxide (H2O2) through an electrochemical oxygen reduction reaction (ORR) is a safe, green strategy and a promising alternative to traditional energy-intensive anthraquinone processes. Air and renewable power could be utilized for on-site and decentralized H2O2 production, demonstrating significant application potential. Currently, single atom catalysts (SACs) have demonstrated significant advantages in the catalytic production of H2O2 in 2e− ORR. However, the selectivity of SACs in ORR once puzzled researchers. This article reviews the research on the development and achievements of H2O2 production by SACs catalysis in recent years. Especially, the structure–performance relationship is a guide to designing new SACs. Combining advanced characterization techniques and theoretical calculation methods, researchers have a clearer and more thorough understanding of the impact of the atomic interface of SACs on ORR catalytic performance. The coordination moiety formed between the active metal center atom and the support seriously determines the selectivity of SACs, mainly manifested in the adsorption of *OOH intermediates. Particularly, the atomic interface of metal atoms together with O/N co-coordination exhibit high selectivity and mass activity, and heteroatoms or functional groups on carbon supports present synergistic effects to promote the production of H2O2 in 2e− ORR. Fine and accurate regulation of the atomic interface of SACs directly affects the 2e− ORR performance of the catalysts. Therefore, it is important to deeply understand the atomic interface of SACs and contribute to the development of novel catalysts.