Group B Streptococcus (GBS) is a leading cause of preterm labor, stillbirth, fetal injury, and neonatal infections, although infections in non-pregnant adults are rising in incidence. While GBS asymptomatically colonizes the female genital and gastrointestinal tracts, ascension to the uterus during pregnancy and delivery can cause invasive disease and adverse neonatal outcomes. The novel protein subunit vaccine GBS-NN, derived from portions of the GBS surface alpha-like proteins Alpha C and Rib, has been tested in a human clinical trial for safety and immunogenicity. Despite these advances, recruitment of pregnant cohorts and measuring vaccine efficacy against adverse birth outcomes is challenging, imposing major roadblocks to GBS vaccine development. Here, we tested GBS-NN vaccine efficacy using three relevant murine models that recapitulate human GBS infection. We observed that immunization by GBS-NN led to robust production of vaccine-specific antibodies compared to adjuvant controls. These antibodies bound not only purified GBS-NN antigen, but also surface expressed Alpha C and Rib on GBS clinical strains. Notably, immunized mice exhibited reduced bacterial burden following GBS systemic challenge. Although GBS-NN immunization did not eliminate GBS from maternal or fetal tissues in a pregnancy model of infection, it effectively reduced rates of intrauterine fetal death. Additionally, neonatal mice born to GBS-NN immunized dams exhibited improved survival following intranasal GBS challenge. Together, these findings demonstrate the efficacy of the GBS-NN vaccine against GBS systemic and pregnancy-associated infections. Our data suggest that maternal GBS-NN vaccination may facilitate the transfer of maternal vaccine-specific antibodies that may help to protect highly susceptible human neonates from GBS invasive infections.