Syphilis can be transmitted by pregnant women to their children and is a public health problem in Africa. A cross-sectional survey was conducted in 24 antenatal clinics from 2002 to 2003 and increased to 30 sites from 2005 to 2011. Participants were tested for syphilis and HIV. Multi-variate logistic regression was performed to identify risks associated with syphilis and its co-infection with HIV. Results showed that syphilis decreased from 3.8% in 2002 to 2.0% in 2011. Syphilis in the HIV-infected participants increased from 6.0% in 2002 to 10.8% in 2011, but decreased from 3.7% to 1.7% in the HIV-negative participants. In 2011, syphilis in urban participants was 2.7% and 1.4% in rural ones. HIV-infected participants screened positive for syphilis more frequently in both rural (aOR = 3.64 [95% CI: 1.56%-8.51%]) and urban areas (aOR = 7.26 [95% CI: 5.04%-10.46%]). Older participants (25-49 years) residing in urban areas (aOR = 0.43[95% CI: 0.32%-0.58%]) and women with secondary or high education (aOR = 0.35[95% CI: 0.20%-0.62%]) were less likely to screen positive for syphilis. HIV-syphilis co-infection was more likely in women residing in urban areas (aOR = 8.32[95% CI: 3.54%-19.56%]), but less likely in women with secondary/high education (aOR = 0.11[95% CI: 0.01%-0.77%]). In conclusion, syphilis increased in HIV-positive pregnant women, but decreased in HIV-negative women. Positive HIV status and young age were associated risks for syphilis. HIV-syphilis co-infection was associated with a lower level of education and urban residence.