Despite the advancement of early childhood caries (ECC) prediction and treatment, ECC remains a significant public health burden in need of more effective preventive strategies. Pregnancy is an ideal period to promote ECC prevention given the profound influence of maternal oral health and behaviors on children’s oral health. However, studies have shown debatable results with respect to the effectiveness of ECC prevention by means of prenatal intervention. Therefore, this study systematically reviewed the scientific evidence relating to the association between prenatal oral health care, ECC incidence, and Streptococcus mutans carriage in children. Five studies (3 randomized control trials, 1 prospective cohort study, and 1 nested case-control study) were included for qualitative assessment. Tested prenatal oral health care included providing fluoride supplements, oral examinations/cleanings, oral health education, dental treatment referrals, and xylitol gum chewing. Four studies that assessed ECC incidence reduction were included in meta-analysis using an unconditional generalized linear mixed effects model with random study effects and age as a covariate. The estimated odds ratio and 95% confidence intervals suggested a protective effect of prenatal oral health care against ECC onset before 4 years of age: 0.12 (0.02, 0.77) at 1 year of age, 0.18 (0.05, 0.63) at 2 years of age, 0.25 (0.09, 0.64) at 3 years of age, and 0.35 (0.12, 1.00) at 4 years of age. Children’s S. mutans carriage was also significantly reduced in the intervention group. Future studies should consider testing strategies that restore an expectant mother’s oral health to a disease-free state during pregnancy.