Passive transfer experiments established the protective role of antibody in immunity against malaria over half a century ago but the mechanisms that underpin protection are still debated. The inhibition of erythrocyte invasion is widely assumed to be the best correlate of antibody-mediated protection. We first demonstrate the power of contemporary controlled human malaria infection studies to clearly distinguish protected from susceptible volunteers. We then show IgG Fc-dependent effector mechanisms involving complement, natural killer cells, neutrophils and monocytes are much stronger correlates of protection than the widely accepted of inhibition of erythrocyte invasion. We found that the breadth of IgG Fc-dependent activity was the strongest predictor of protection. Our data suggest that a structure & Fc-function guided approach to malaria vaccine development may be beneficial.