<p>High-entropy alloys (HEAs) have emerged as a promising class of multi-element materials with tunable physicochemical properties, making them highly attractive for catalytic applications. However, achieving atomic mixing and precise control over atomic arrangements remains challenging due to variations in metal precursor reduction kinetics and the intrinsic structural preferences of the constituent elements. This review explores seed-mediated synthesis as an effective strategy for fabricating HEA atomic layers with well-defined facets, compositions, and crystal structures. By leveraging dropwise precursor addition, the formation of solid-solution HEAs is promoted while mitigating phase segregation caused by variations in precursor reduction rates. The integration of epitaxial growth on well-defined seed templates enables facet-specific deposition of HEA atomic layers while preserving surface atomic arrangements consistent with the seeds. Additionally, advances in composition tuning and structural regulation are examined by systematically controlling precursor selection, reaction temperature, and seed properties. Finally, we highlight the catalytic implications of these HEA atomic layers, emphasizing the necessity of in situ spectroscopy and theoretical modeling to elucidate the complex reaction mechanisms associated with their multi-element active sites. By bridging synthetic strategies with catalytic functionality, this review provides a comprehensive framework for designing next-generation HEA nanomaterials, offering insights into their potential applications in energy conversion and storage technologies.</p> Graphical Abstract <p></p>