Data for the extraction of chromium, Cr(VI), from aqueous acidic chloride and nitrate solutions by Alamine 300 (tertiary amine)/xylene and di-n-octyl amine (DOA)/xylene solvent systems (298 K) have been subjected to formulation of an optimization structure for an effective Cr(VI) separation. The optimization approach uses a derivative variation method to efficiently identify the optimization range through analyzing the first-order derivatives of the optimized quantity and the nonlinear deviation profile of the derivative value. The main characteristics of it are simplicity and suitability for generalization. Optimum Cr(VI) removal efficiencies, defined both experimentally and analytically, range from about 70 to 90% for Alamine 300 and from 50 to 70% for DOA, being dependent about equally strongly on the types and concentration levels of the amine, acid, and the transferred Cr(VI) species. These dependencies are rationalized in terms of the interactions that take place in the equilibrium phases. Three independent variables, i.e. the concentrations of the amine, acid, and Cr(VI), are adequate for expressing the nonlinear dependence of the optimized extraction factor (E, Z(t)) on the properties of relevant system. Modeling efforts based on the LSER (linear solvation energy relation) principles and the mass-action law methodology have shown considerable success. The proposed LSER-based solvation model using nine physical descriptors of the solvent and ion provides relatively reliable fits with a mean error of 9%, and satisfies established limiting behavior of the physical event. A critical comparison of the present method with the other commonly used reactive extraction methods on an efficiency basis has been carried out.