Background: Seasonal influenza A(H3N2) exhibits rapid global lineage turnover driven by continuous antigenic evolution. However, the emergence of newly dominant H3N2 lineages remains incompletely understood.

Methods: We combined large-scale genomic surveillance with phylogenetic reconstruction, temporal mutation dynamics analyses, geographic dissemination analyses, and structural characterization to investigate emergence and global expansion of the H3N2 K lineage. A total of 170,793 complete human H3N2 hemagglutinin (HA) sequences collected globally between 1992 and 2026 were retrieved from GISAID.

Results: We found that the K lineage rapidly replaced previously co-circulating H3N2 J.2 sublineages within a single influenza season. Its global expansion was associated with a non-canonical dissemination pattern centered on the United States rather than the traditional East-Southeast Asia (E-SEA) source system. Temporal mutation dynamics analyses of global surveillance data showed that K-lineage-defining substitutions were first detected in the United States and Japan. Despite accumulation of multiple antigenic-site substitutions, structural analyses suggested preservation of overall HA structural stability, with differential compatibility across pre-existing antibodies rather than complete antibody escape.

Conclusions: Our findings expand current understanding of how globally dominant H3N2 variants emerge and suggest that geographically distributed evolutionary assembly may represent an important pathway in contemporary influenza evolution.