Objective To assess potential determinants of uptake and highlight lessons learnt from the implementation of intermittent preventive treatment (IPTp), given to pregnant women as early as possible during the second trimester in Zambia. Methods Data from four national malaria surveys (2006, 2008, 2010, 2012) were reviewed, and proportions of pregnant women attending antenatal clinics (ANCs) who received two or more doses of sulfadoxine–pyrimethamine (IPTp2) were compared by place of residence, education level, and wealth status. Malaria cases and deaths in pregnant women, from Health Information Management System 2011–2013, were analyzed to determine malaria burden in pregnancy in Zambia. A multiple logistic regression model was applied to identify potential determinants of IPTp uptake. Results The proportion of pregnant women who took IPTp at ANCs increased from near zero at inception in 2001 to 61.9% in 2006; and to 72% by 2012 (P < 0.001), and overall the uptake was 1.41 times higher in 2012 compared to 2006. From 2006 to 2012, IPTp2 uptake among women with no formal education increased from 51% to 68% (P < 0.1). Likewise, uptake among pregnant women with the lowest wealth index increased from 58.2% to 61.2%. By 2012, IPTp uptake among pregnant women within the lowest wealth index increased to a similar level as the women with high wealth index (P = 0.05). Incidence of malaria cases, hospital admissions and mortality during pregnancy decreased between 2011 and 2013. Overall, increased IPTp uptake was associated with being in urban areas (OR = 1.56, 95% CI: 1.39–1.74), having college (OR = 1.83, 95% CI: 1.25–2.75) or secondary education (OR = 1.68, 95% CI: 1.44–1.96) or of being of higher wealth status (OR = 1.86, 95% CI: 1.60–2.17). Conclusions Zambia has increased IPTp uptake through ANC for all women. The malaria control program has contributed to increasing access to health services and reducing demographic and socioeconomic disparities.