Abstract: Energy is foundational for the advancement of human society, occupying a pivotal role in the national economy. Single-atom catalysts (SACs) are a promising catalyst material in the chemistry and energy fields owing to their high activity, high efficiency, adjustable electronic structure, and low price. Therefore, the development of SACs with high activity, superior stability, and low cost holds significant practical importance. In particular, asymmetric coordination structures in SACs have gained attention over traditional M–N₄ active sites in terms of catalytic performance. In the context of the oxygen reduction reaction (ORR), a key step in fuel cell technology, SACs with asymmetric coordination structures have demonstrated enhanced catalytic efficiency by optimizing the electronic properties of active sites. This leads to a substantial reduction in activation energy, resulting in improved current densities and energy conversion efficiencies, thus accelerating the commercialization of fuel cells. Similarly, in the CO₂ reduction reaction (CO₂RR), these catalysts can fine-tune the adsorption and activation of CO₂ molecules, promoting the selective and efficient conversion of CO₂ into valuable chemicals such as methanol and carbon monoxide. This capability offers significant potential for carbon recycling technologies. Moreover, asymmetric SACs have shown remarkable promise in addressing environmental challenges, particularly in the nitrate reduction reaction (NO₃RR) by efficiently converting harmful nitrates into inert nitrogen, which contributes to environmental protection and water quality improvement. In general, axial coordination in electrocatalysts enhances electrocatalytic reactions such as CO₂RR and ORR by fine-tuning the electronic structure of metal centers to optimize reaction kinetics and stabilize the catalyst. This coordination facilitates the efficient desorption of catalytic intermediates while mitigating side reactions, leading to improved catalyst durability and enhanced electrochemical stability. This review provides a comprehensive overview of several typical asymmetric SAC structures, including M–N₄–Y (where Y represents an axial heteroatom), M–N_x–Y (where Y is a nonmetal atom), M–N_x, and M–M configurations. We systematically review the controlled synthesis of these advanced catalysts, highlighting their recent progress and applications in electrocatalytic reactions such as ORR, CO₂RR, and NO₃RR. Finally, the challenges and future prospects of SACs in terms of synthesis, performance, and underlying mechanisms are critically discussed. While SACs have made significant progress, issues such as the precise control of atomically dispersed sites, stability under reaction conditions, and understanding the detailed catalytic pathways remain key challenges. This review aims to provide valuable insights and guidance for the continued advancement of SACs to optimize their practical applications and accelerate their integration into large-scale catalytic processes.