Single-atom catalysts (SACs) reveal great potential for application in catalysis due to their fully exposed active sites. In general, single atoms (SAs) and the coordination substrates need to have strong interactions or charge transfer to ensure the atomic dispersion, which requires the selection of a suitable substrate to stabilize the target atoms. Recent studies have demonstrated that amorphous materials with abundant defects and coordinatively unsaturated sites can be used as substrates for more efficient capturing SAs, further enhancing the catalytic performance. In this review, we discuss recent research progress of SAs loaded on amorphous substrates for enhanced catalytic activity. Firstly, we summarize the commonly used amorphous substrates for stabilizing SAs. Subsequently, we present several advanced applications of amorphous SACs in the field of catalysis, including electrocatalysis and photocatalysis. And then, we also clarify the synergistic mechanism between SAs and amorphous substrate on catalytic process. Finally, we summarize the challenges with our personal views and provide a critical outlook on how amorphous SACs continue to evolve.