Single superphosphate (SSP) is manufactured by direct reaction between phosphate rock concentrates and sulfuric acid in the presence of water in complex long-lasting reactions. Approximately 95% of the phosphate concentrates used in Brazil are obtained from igneous rocks. One of the main contaminants in these mines is iron oxide, in which total removal is technically and economically unfeasible. High concentrations of iron oxides in SSP production may result in the formation of water-insoluble iron phosphates, which are partially insoluble in neutral ammonium citrate (NAC) and may possess lower agronomic efficiency. To enable the production of SSP from rocks with higher concentrations of iron contaminants, a Central Composite Design was executed to study the effects of iron oxide concentrations associated with the usual reaction variables in SSP production. By adopting optimized reaction conditions, it is possible to maximize the NAC solubility of SSP with conversions nearing 100% with phosphate concentrates containing up to 14.7% of Fe 2 O 3 . The high conversions achieved partially offset the lower total P 2 O 5 contents in the product, demonstrating technical feasibility for the industrial use. This study was conducted in Brazil's largest SSP production plant, with an installed capacity of 1.2 million tons per year, in order to generate process parameters for a regular industrial operation, thus allowing the use of phosphate rocks with higher iron concentrations.