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Background Tanzania adopted the revised World Health Organization policy in 2013 recommending a minimum of ≥3 doses of Intermittent Preventive Treatment during pregnancy with Sulfadoxine-Pyrimethamine (IPTp-SP) to protect against malaria. A study in Tanzania in 2014 reported low (9%) uptake. We investigated health workers knowledge about IPTp-SP and factors that influenced uptake of > 3 doses of IPTp-SP among pregnant women. Methods We conducted a cross-sectional study in 2017 among post-delivery women and health care workers from nine randomly-selected public health facilities in three Districts of Arusha Region. Probability proportional to size methodology was used to determine number of participants per facility. We used a structured questionnaire to collect socio-demographic and obstetric data, information on doses of SP received, and knowledge of SP for IPTp. Health care workers were interviewed about their knowledge for IPTp- SP and challenges encountered in its uptake and use. Results We interviewed 556 persons (median age 26 years, range 16–42 years) with the response rate of 99.3%. Of these, 484 (87.1%) had > 3 Antenatal Care (ANC) visits. A total of 402 (72.3%) were multigravida with 362 (65.1%) having given birth at least once. Of the 556 participants, 219 (39.4%) made their first ANC booking at > 3 doses of SP-IPTp. Factors associated with uptake of > 3 doses of IPTp-SP included having secondary or higher education [Adjusted Odds Ratio (AOR) =1.6, 95%CI 1.1–2.4], attending ≥4 ANC visits [AOR = 3.1, 95%CI 2.1–4.6], having first antenatal booking at Conclusions Fewer than half of the women interviewed reported uptake of > 3 doses of IPTp-SP. That is below the Tanzania national target of 80%. Making > 4 ANC visits, having secondary or higher education, making an early first ANC visit and having adequate knowledge on IPTp-SP promoted uptake of > 3 doses. Further qualitative studies are needed to explore factors that might contribute to low uptake of SP.