Transition metal single-atom catalysts (SACs) have been a hot area of research in the field of electrocatalytic oxygen reduction reaction (ORR) currently. In this review, we reported the recent advances in transition metal single-atom supported by two-dimensional (2D) materials as catalysts for oxygen reduction reaction with high performance. Due to its large surface area, uniformly exposed lattice plane and adjustable electronic state, 2D materials are ideal supporting materials for exploring the actual ORR active sites and surface reactions. The rational design principles and synthetic strategies of transition metal SACs supported by 2D materials are systematically introduced while the identi?cation of active sites, their possible catalytic mechanisms as well as the future perspectives of transition metal SACs supported by 2D materials for ORR applications are discussed. Finally, according to the current development trend of ORR catalysts, we summarize the future opportunities and challenges of transition metal SACs supported by 2D materials.