Congenital syphilis (CS) continues to pose a significant global challenge. There has been a marked increase in reported cases in the United States, with 102.5 cases per 100,000 live births in 2022 compared with 11.6 cases per 100,000 live births in 2014. Congenital syphilis can lead to a range of severe complications, including premature birth, intrauterine growth restriction, miscarriage, perinatal death, stillbirth, and postnatal complications that may persist into later life. Maternal/parental factors such as age, race/ethnicity, occupation, income level, access to health care services, and incarceration have been linked to higher rates of CS. In addition, pregnant individuals who engage in high-risk behaviors such as sex work, having multiple sexual partners, or substance use are at a higher risk of exposure and subsequent infection. Routine screening for syphilis during pregnancy is crucial for its detection, timely management, and prevention of CS. The asymptomatic nature of the latent stage of syphilis further underscores the importance of prenatal syphilis screening. Studies in various countries have shown that early or first antenatal care visit screening for CS is cost-effective. This review article critically evaluates the current knowledge of CS in the United States, including its prevalence, social determinants of health, prevention efforts, challenges, the significance of screening, and the call to action to address the rising trend. (See Graphical Abstract)