Sodium-K, Na-Ca, Na-Mg, and Na-Sr exchange isotherms were performed at a total Cl concentration of about 0.005 mol L−1 on the fine fraction (<2 μm) of MX80 montmorillonite, mixed-layer illite smectite minerals (IS), and clayey stones from European underground research laboratories. The derived selectivity coefficients for Na-K, Na-Ca, Na-Mg, and Na-Sr were found to vary very significantly as a function of the exchanger composition. A model was built to reproduce the data, taking into account the change of selectivity coefficient as a function of the exchanger composition of smectite. Model parameters were fitted using data from the present study and data from the literature obtained on smectite minerals. The addition of parameters for cation–anion pairs was found to improve the fitting results. The model was then successfully tested to reproduce published cation-exchange features on natural clayey materials and soils suspended in fresh or saline water. Finally, it is shown that the simple combination of this smectite exchange model with a previously published illite exchange model is quite successful although perfectible in reproducing exchange data on IS.