A common clone (ET3) of Staphylococcus aureus is responsible for a large proportion of cases of bovine mastitis and occasionally causes zoonotic infections of humans. In the present study, we report the identification of a virulent clonal subtype (ST151) of ET3, which resulted in increased tissue damage and mortality in a mouse model of mastitis. ST151 has undergone extensive diversification in virulence and regulatory-gene content, including the acquisition of genetic elements encoding toxins not made by other ET3 strains. Furthermore, ST151 had elevated levels of RNAIII and cytolytic toxin-gene expression, consistent with the enhanced virulence observed during experimental infection. Previously, the ST151 clone was shown to be hypersusceptible to the acquisition of vancomycin-resistance genes from Enterococcus spp. Taken together, these data indicate the emergence of a virulent subtype of the common ET3 clone, which could present an enhanced risk to public health.