Two-dimensional (2D) layered materials have proven to be crucial platforms for anchored individual and isolated metal atoms acting as active single atom catalysts (SACs). Therefore, an accurate location of single atoms is essential for understanding the reaction mechanism and design of SACs anchored at 2D layered materials. However, the preparation of SACs with a precise location remains a great challenge. This review highlights recent advances in the preparation, characterization, and catalytic performance of SACs, focusing on single atoms anchored at 2D layered materials beyond graphene. These 2D materials include transitional metal dichalcogenides, layered double hydroxides, and MXenes. Importantly, the topic of impurities is discussed because these can be present at an even higher percentage than the single atoms at 2D layered materials. A variety of electrochemical energy applications are discussed in which SACs have a crucial role, including water splitting and carbon dioxide reduction. Finally, this review provides the latest applications and developments perspective of single metal atoms on 2D surfaces, which offers a unique opportunity to tune active sites and optimize the activity, selectivity, and stability of electrocatalysts.