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Congenital syphilis (CS) is a significant public health problem in Brazil. Despite efforts to increase syphilis testing and treatment among pregnant women, rates of CS in the country remain high. We conducted a retrospective case-control study to identify potential associations between the mothers’ sociodemographic characteristics, clinical factors related to the current and previous pregnancies, and the occurrence of CS among newborns in Fortaleza, a populous city with one of the highest incidences of CS in Brazil. Data from newborns diagnosed with CS between 2017 and 2020 were extracted from SINAN, the national database for notifiable diseases. Data from women who had delivered an infant with CS were extracted from SINASC, the national database for registration of live births, and linked with their infant’s data. CS cases and non-CS controls were matched by year of birth at a ratio of 1:3 respectively. Potential associations were estimated using a multivariate regression model accounting for sociodemographic, obstetric, and antenatal care-related factors. Epidemiological data from 8,744 live births were included in the analysis, including 2,186 cases and 6,588 controls. The final multivariate regression model identified increased odds of delivering an infant with CS among pregnant women and girls aged below 20 years (OR 1.29), single women (OR 1.48), women who had less than 8 years of formal education (OR 2.42), women who delivered in a public hospital (OR 6.92), women who had more than 4 previous pregnancies (OR 1.60), and women who had one or more prior fetal loss (OR 1.19). The odds of delivering an infant with CS also increased as the number of antenatal visits decreased. Women who did not attend any antenatal visits had 3.94 times the odds of delivering an infant with CS compared to women who attended 7 or more visits. Our study found that increased odds of delivering an infant with CS were highly associated with factors related to socioeconomic vulnerability. These determinants not only affect the access to essential antenatal care services, but also the continuity and quality of such preventive measures. Future policies aimed at reducing the incidence of CS should not only target those pregnant women and adolescents with identifiable risk factors for testing, but also assure high quality care, treatment and follow-up for this group.