Abstract The search for constructing high-performance catalysts is an unfailing topic in chemical fields. Recently, we have witnessed many breakthroughs in the synthesis of single-atom catalysts (SACs) and their applications in catalytic systems. They have shown excellent activity, selectivity, stability, efficient atom utilization and can serve as an efficient bridge between homogeneous and heterogenous catalysis. Currently, most SACs are synthesized via a bottom-up strategy; however, drawbacks such as the difficulty in accessing high mass activity and controlling homogeneous coordination environments are inevitably encountered, restricting their potential use in the industrial area. In this regard, a novel top-down strategy has been recently developed to fabricate SACs to address these practical issues. The metal loading can be increased to 5% and the coordination environments can also be precisely controlled. This review highlights approaches to the chemical synthesis of SACs towards diverse chemical reactions, especially the recent advances in improving the mass activity and well-defined local structures of SACs. Also, challenges and opportunities for the SACs will be discussed in the later part.