In the present study, the extraction of zinc(II) and cadmium(II) with mixtures of neutral organophosphorus extractants (aliphatic trialkyl phosphine oxide, Cyanex 923, or branched cyclic trialkyl phosphine oxide, Cyanex 925) and amine extractants (N,N-di(1-methylheptyl) acetamide, N503, or trialkyl amine, N235) has been investigated. Synergistic effects were observed for zinc(II) with Cyanex 923 + N503 and for cadmium(II) with Cyanex 923 N235 and Cyanex 925 + N235. However, the other mixing systems do not have synergistic effects on zinc(II) and cadmium (II). According to the different extraction effects, the separation possibilities of zinc(II) and cadmium(II) are discussed. The extraction mechanisms have been studied with the methods of slope analysis and constant moles in the three synergistic systems. The extracted compounds, the equilibrium constants, and thermodynamic functions have also been determined.