The importance of the oxygen reduction reaction (ORR) in fuel cells and zinc-air batteries is self-evident, and effective catalysts could significantly improve the catalytic efficiency of ORR. Single-atom catalysts are gaining increasing interest due to their high atom efficiency and effective catalytic performance compared to other catalyst types. While the optimal loading of catalytic sites in single-atom catalysts significantly influences their catalytic efficiency. However, creating stable single-atom catalysts with high-loading remains a difficult task. Therefore, we showcase and describe the latest developments in techniques for producing single-atom catalysts with high-loadings. In addition, the performance of noble metal, non-precious metal, and diatomic catalysts in ORR processes is summarized. What’s more, the key difficulties and opportunities in the sector are demonstrated by examining the synthesis techniques and evaluating the performance and structure. This review will help researchers to advance the research process of high-loading single-atom catalysts and accelerate their practical application in the field of ORR research.