The overall objective of this study is to model and optimize the elimination of lead ions from aqueous solutions by inactive brewer's yeast in a batch reactor. Optimization of the most important factors directly affecting the adsorption of lead onto the biosorbent was carried out by using a 2 k factorial experiment. This later is performed to ascertain the effect of solution pH, initial concentration of lead ions, inactive brewer's yeast dose, temperature, and their cross-influence on the lead adsorption yield. The results suggest that the most influential factor is the solution pH followed by the initial concentration of lead ions, inactive brewer's yeast dose, and temperature. The results have shown also the interaction between solution pH/initial lead concentration and initial lead concentration/inactive brewer's yeast dose with different degrees of importance. The optimal values of solution pH, initial concentration of lead ions, biosorbent dose, and temperature are 4, 53.75 mg·L–1, 2.3 ≤ m ads ≤ 2.5 g·L–1, and 305 ≤ T ≤ 308 K, respectively. Adsorption parameters for the Langmuir and Freundlich isotherm models were determined at different temperatures between (298 and 308) K. According to the biosorption isotherm plots, the Freundlich model describes perfectly the sorption of lead onto inactive brewer's yeast.