SARS-CoV-2 has caused the global COVID-19 pandemic. Although passively delivered neutralising antibodies against SARS-CoV-2 show promise in clinical trials, their mechanism of action in vivo is incompletely understood. In this article, the authors defined correlates of protection of neutralising human monoclonal antibodies (mAbs) in SARS-CoV-2-infected animals. Whereas Fc effector functions are dispensable when representative neutralising mAbs are administered as prophylaxis, they are required for optimal protection as therapy. When given after infection, intact mAbs reduce SARS-CoV-2 burden and lung disease in mice and hamsters better than loss-of-function Fc variant mAbs. Fc engagement of neutralising antibodies mitigates inflammation and improves respiratory mechanics, and transcriptional profiling suggests these phenotypes are associated with diminished innate immune signaling and preserved tissue repair. Immune cell depletions establish that neutralising mAbs require monocytes and CD8+ T cells for optimal clinical and virological benefit. Thus, potently neutralising mAbs utilise Fc effector functions during therapy to mitigate lung infection and disease.