Despite relatively simple prevention and treatment, syphilis remains a major social and public health concern worldwide, particularly in developing nations. To estimate the prevalence and to determine the sociodemographic factors associated with syphilis infection among antenatal-care (ANC) attendees in Meghalaya, India. A facility-based cross-sectional study was conducted utilizing National HIV Sentinel Surveillance of Meghalaya, January-March 2017. Pregnant women aged 15-49years (n = 3015) were recruited consecutively, interviewed, and tested for syphilis by Venereal Disease Research Laboratory test in eight selected ANC sites representing all districts of Meghalaya. Prevalence of syphilis was found to be 1.03 % (95% CI = 0.67-1.39) (31/3015). Prevalence was maximum among illiterates with gradual lowering of adjusted odds ratio (AOR) with improvement of education. Women whose husbands had no income were associated with higher risk (AOR = 4.97, 95% CI = 1.11-22.20) of syphilis. Significant risk (OR = 2.42, 95% CI = 1.02-5.74) was also observed with Jaintia Hills residents as compared to Garo Hills. As high prevalence of gestational syphilis was identified in Meghalaya along with important sociodemographic predictors, evidence to policy translation is required at state and national level to scale up prevention, screening, and management of syphilis.