Background The Uganda National Malaria Control Programme recognizes the importance of minimizing the effect of malaria among pregnant women. Accordingly, strategies including intermittent preventive treatment of malaria in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) have been scaled up. Uptake of IPTp-SP among pregnant women in Uganda, aged 15–49 years who had had a live birth 2 years preceding the 2016 Uganda Demographic and Health Survey (UDHS) was determined and factors associated with the uptake of optimal IPTp-SP doses were identified. Methods This was a secondary analysis of the UDHS 2016 dataset. The outcome variable was uptake of IPTp-SP doses among women 15–49 years old who had had a live birth 2 years preceding the survey. Independent variables were residence type, age, marital status, education, wealth status, region of residence, parity, number of antenatal care (ANC) attendance, timing to first ANC visit, and exposure to messages through radio. Logistic regression was used to identify factors associated with the uptake of optimal IPTp-SP doses. Results Uptake of three or more doses of IPTp-SP was 18%. The likelihood of taking optimal doses of IPTp-SP was increased among those who had attained a secondary-level education (aOR: 1.5, 95% CI 1.04–2.15), those who attended ANC ≥ 4 times (aOR: 1.34, 95% CI 1.12–1.60), and those exposed to radio messages (aOR: 1.23, 95% CI 1.02–1.48). Among those in the age category > 34 years (aOR: 0.70, 95% CI 0.53–0.92), and those who attended first ANC in the third trimester of pregnancy (aOR: 0.58, 95% CI 0.38–0.87) the odds of uptake were decreased. Conclusions Education status, exposure to radio messages about health and frequency of ANC attendance were associated with increased uptake while timing of first ANC attendance and being > 34 years were associated with decreased uptake. The findings suggest a need to strengthen behaviour change communication among women of child-bearing age in order to improve uptake of IPTp-SP during pregnancy.