Over the past 2 decades, congenital syphilis cases have risen 11-fold in the United States. Although disparities across geography, race, and ethnicity exist, lack of timely screening or treatment is identified in 88% of cases nationally. Congenital syphilis is a public health and medical problem rooted in systematic and societal structural determinants of health and health care limitations. Early syphilis in pregnancy leads to congenital syphilis if untreated in 50% to 70% of cases, with risk for fetal demise, and among survivors, congenital anomalies, organ damage, and central nervous system disease. Prevention of congenital syphilis lies in early detection and treatment in pregnant persons. In this narrative review, we describe the evolving epidemiology of syphilis and congenital syphilis, highlighting unique aspects among women. We explore the role of novel screening and treatment strategies, public health policy, and medical considerations in terms of congenital syphilis prevention. Readers of this review will understand congenital syphilis as a complex public health and medical disease that can be prevented through innovative and coordinated strategies in public health policy, expanded screening, and research opportunities.