Prenatal viral infections can lead to neurodevelopmental disorders in offspring. However, the impact of maternal perturbations on the developmental trajectory of macrophages in the fetal brain remains unclear. Here, we demonstrate that inflammatory decidual natural killer (NK) cells, triggered by early pregnancy insults, drive neurodevelopmental and behavioral disorders in offspring. Extracellular granzyme B (GzmB), predominantly released by the maternal CD49a⁺ NK subset under type I interferon stimulation, crosses the maternal-fetal barrier and promotes interferon-stimulated genes (ISGs)-expressing macrophage accumulation and microglia activation. Targeting extracellular GzmB through the systemic administration of the serine protease inhibitor Serpina3n or genetic ablation of GzmB in maternal NK cells mitigates neuroimmune disorders in the fetal brain. These findings suggest that exposure to an insulted maternal milieu can reprogram the NK cell immune state, which has a crucial impact on neuroimmune disorders in the fetus and shaping vulnerability in offspring later in life.