We estimate the seroprevalence of IgG antibodies to varicella zoster virus (VZV) based on the first serological study in a cohort of pregnant women and newborns from the Aburrá Valley (Antioquia-Colombia) who attended delivery in eight randomly chosen hospitals. An indirect enzyme immunoassay was used to determine anti-VZV IgG antibodies. Generalized linear models were constructed to identify variables that modify seropositivity. In pregnant women, seropositivity was 85.8% (95% CI: 83.4–85.9), seronegativity was 12.6% (95% CI: 10.8–14.6), and concordance with umbilical cord titers was 90.0% (95% CI: 89–91). The seropositivity of pregnant women was lower in those who lived in rural areas (IRR: 0.4, 95% CI: 0.2–0.7), belonged to the high socioeconomic status (IRR: 0.4, 95% CI: 0.2–0.7), and had studied 11 years or more (IRR: 0.6, 95% CI: 0.4–0.8). Among newborns, seropositivity was lower in those who weighed less than 3000 g (IRR: 0.8, 95% CI: 0.6–1.0). The high seropositivity and seronegativity pattern indicates the urgent need to design preconception consultation and vaccination reinforcement for women of childbearing age according to their sociodemographic conditions, to prevent infection and complications in the mother and newborn.