The intermittent administration of seasonal malaria chemoprevention (SMC) is recommended to prevent malaria among children aged 3–59 months in areas of the Sahel subregion in Africa. However, the cost-effectiveness and cost savings of SMC have not previously been evaluated in large-scale studies. We did a cost-effectiveness and cost-savings analysis of a large-scale, multi-country SMC campaign with sulfadoxine–pyrimethamine plus amodiaquine for children younger than 5 years in seven countries in the Sahel subregion (Burkina Faso, Chad, Guinea, Mali, Niger, Nigeria, and The Gambia) in 2016. The total cost of SMC for all seven countries was $22·8 million, and the weighted average economic cost of administering four monthly SMC cycles was $3·63 per child (ranging from $2·71 in Niger to $8·20 in The Gambia). Based on 80% modelled effectiveness of SMC, the incremental economic cost per malaria case averted ranged from $2·91 in Niger to $30·73 in The Gambia. The estimated total economic cost savings to the health systems in all seven countries were US$66·0 million and the total net economic cost savings were US$43·2 million. Our interpretation is that SMC is a low-cost and highly cost-effective intervention that contributes to substantial cost savings by reducing malaria diagnostic and treatment costs among children.