Malaria in pregnancy is a leading cause globally of poor maternal health, and low birth weight and premature delivery of neonates leading to greatly increased mortality and morbidity. Currently available tools have had some impact on reducing the severity of disease, and a greater understanding of how immunity against MiP develops, and mechanisms and targets of immunity, may enable the development of new interventions and vaccines. MiP is characterised by the accumulation of Plasmodium falciparum-infected red blood cells (pRBCs) in the placenta that can trigger detrimental inflammatory responses. Infection and adverse outcomes are less prevalent with successive pregnancies partly due to the acquisition of specific antibodies. Acquired antibody responses are predominantly of the immunoglobulin IgG1 and IgG3 subtypes, which can potentially activate the complement system, but a role for antibody-complement mechanisms in naturally-acquired immunity against MiP has not been previously tested. In a longitudinal cohort of 350 pregnant women from a malaria-endemic region in Papua New Guinea, we have established that acquired antibodies among pregnant women promote the deposition of complement on the surface of placental-binding pRBCs. Using whole blood assays, we found that complement fixation greatly enhanced opsonic phagocytosis of pRBCs by monocytes, a mechanism likely to provide protection against MiP. Furthermore, antibodies that can fix complement on pRBCs inhibit their binding to placental receptors. Using genetically engineered P. falciparum, we identified the parasite antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) as the major target of complement-fixing antibodies. Analysis of the longitudinal data found an association between complement-fixing antibodies and protection against placental malaria and reduced placental parasitaemia. These findings provide new insights into the mechanisms mediating immunity to malaria in pregnancy and have the potential to advance vaccine development.