Influenza H3N2 subclade K (J.2.4.1) is a genetic branch of H3N2 with 11 mutations in hemagglutinin and currently represents the dominant circulating influenza strain. We evaluated antibody responses to H3N2 subclade K before and after influenza vaccination in 46 healthy individuals. Our data show that baseline antibody responses to two H3N2 subclade K variants were lower than to other H1N1 and H3N2 strains and that antibody responses following vaccination were also less robust to the H3N2 subclade K variants. These data indicate that the H3N2 subclade K strain partially evades both prior H3N2 immunity and the current inactivated influenza vaccine.