The influences of pH value, Fe3+ mass concentration, and stirring rate and their interactions on the ammonium sulfate crystallization were investigated via cooling crystallization and sieving based on a response surface methodology. An average particle size quadratic orthogonal model and a variation coefficient 2FI orthogonal model were proposed. The interactions among the various factors were analyzed. The results show that pH value (A) > stirring rate (C) > Fe3+ ions concentration (B) is a decreased order for the parameter effects on the average particle size and variation coefficient. Their interactions have a decreased effect order (i.e., AC > BC > AB) on the average particle size and variation coefficient. When pH value is 5.5, stirring rate is 150 r/min, and Fe3+ ions concentration is 0.3 g/L, the average particle size and variation coefficient of the ideal crystals is 0.985 mm and 793.719, respectively.