High-entropy single-atom catalysts (HESACs) represent a paradigm shift in electrocatalyst design, integrating the atomic efficiency of single-atom catalysts (SACs) with the configurational entropy of high-entropy alloys (HEAs). Unlike conventional SACs, HESACs maintain well-defined coordination geometries while leveraging multi-element electronic reconstruction to mitigate the limitations of single metal sites in complex multistep reactions. This review outlines the fundamentals, design principles, and recent synthetic advancements in HESACs, including spatial confinement, laser planting, selective etching, movable-type printing, and pyrolysis, alongside advanced characterization techniques. Performance in key applications, such as HER, ORR/OER, NO₃RR, and Li–S batteries, demonstrates that entropy-driven electronic modulation and multi-site synergy are central to their exceptional activity and durability. Finally, we discuss challenges and future pathways for translating HESACs from fundamental discoveries to practical electrocatalytic applications.