Abstract Background Intermittent Preventive Treatment (IPT) of malaria in pregnancy is a full therapeutic course of antimalarial sulfadoxine-pyrimethamine (SP) medicine given to pregnant women in their second trimester at routine antenatal care visits, regardless of whether the recipient is infected with malaria. Given the negative consequences of malaria in pregnancy, studies on Intermittent Preventive Therapy with Sulfadoxine-Pyrimethamine (IPTp-SP) are important benchmarks for understanding the extent of malaria control and prevention during pregnancy. We, therefore, examined the factors associated with the uptake of IPTp-SP among pregnant women in sub-Saharan Africa. Methods We used data from the current versions of the Malaria Indicators Survey of 12 countries in sub-Saharan Africa. Women aged 15–49 years participated in the surveys. The analyses were carried out using Stata version 14.2. Descriptive (frequencies and percentages) and multilevel regression analyses were carried out. The results of the multilevel regression analysis were presented as adjusted odds ratios (aOR) with 95% confidence intervals (CIs). Results The average prevalence of uptake of IPTp-SP among pregnant women in the studied sub-Saharan African countries was 30.69%, with the highest and lowest prevalences in Ghana (59.64%) and Madagascar (10.08%), respectively. Women aged 40–44 compared to those aged 15–19 (aOR = 1.147, 95%CI = [1.02,1.30) had higher odds of receiving 3 or more doses of IPTp-SP. Women with a secondary/higher level of education compared to those with no formal education (aOR = 1.12, 95%CI = 1.04,1.20] also had higher odds of receiving 3 or more doses of IPTp-SP. Women who were exposed to malaria messages on the radio (aOR = 1.07, 95%CI = 1.02,1.12] and television (aOR = 1.13,95%CI = [1.05,1.21]) had higher odds of receiving 3 or more doses of IPTp-SP compared to those who were not exposed. Conclusion Our study indicates that the uptake of IPTp-SP is relatively low among the countries included in this study, with significant inter-country variations. Higher educational level, exposure to media, low parity, and higher age group were associated with higher odds of optimal IPTp-SP uptake. National policies, programs, guidance services such as information service and counselling and other interventions aimed at improving the coverage and uptake of IPTp-SP must be targeted at women with low level of education, non-exposure to media, high parity, and younger age group to attain the desired outcome.