Significance A panel of 80 human IgA monoclonal antibodies isolated after seasonal influenza virus vaccination was interrogated. We have discovered an IgA monoclonal antibody binding to an epitope for H1N1 viruses at the head–stalk interface that displays antibody-dependent cell-mediated cytotoxicity activity. Also, a mechanism of antibody Fc-mediated effector function activation was refined for influenza virus, which describes that low-affinity Fc receptors require an additional point of contact between influenza HA and its cognate sialic acid-bearing receptor for activation, while high-affinity Fc receptors can be activated without this contact.