In recent years, against the backdrop of widespread administration of acellular pertussis (aP) vaccines, the incidence of pertussis has exhibited a resurgent trend in numerous countries across the globe. Molecular epidemiological studies have revealed that population-level variations have occurred in multiple virulence genes encoding vaccine-associated antigens of Bordetella pertussis (Bp), accompanied by the replacement of dominant clonal lineages, which may be implicated in the phenomenon of "pertussis resurgence". This review summarizes the variation characteristics of major vaccine-associated antigen genes of Bp in recent years, including pertussis toxin promoter (ptxP), pertussis toxin subunit A (ptxA), pertactin gene (prn), filamentous hemagglutinin gene (fhaB), and fimbriae gene (fim), with a focus on the analysis of their evolutionary trends in circulating strains in China and the discrepancies from the antigen components of currently used co-purified acellular pertussis vaccines (cp-ACVs). Available evidence demonstrates that vaccine immune pressure may drive the expansion of non-vaccine-type alleles such as prn deficiency, ptxP3, and ptxA1, while antimicrobial selective pressure facilitates the formation of dominant clonal clusters harboring multiple phenotypic characteristics. The aforementioned structural alterations of antigens may elevate the potential risks of vaccine antigen mismatch and immune escape. Accordingly, sustainable implementation of whole-genome sequencing-based molecular epidemiological surveillance, combined with optimization of vaccine antigen design by integrating host immune response mechanisms, constitutes a crucial strategy to counteract the continuous evolution of Bp and enhance the efficacy of pertussis prevention and control.