In situ XRD and NMR experiments combined with molecular dynamics simulations using the grand canonical ensemble (GCMD) show that cation size, charge and solvation energy play critical roles in determining the interlayer expansion of smectite clay minerals when exposed to dry supercritical CO2 under conditions relevant to the earth’s upper crust, petroleum reservoirs, and geological CO2 sequestration conditions (323 K and 90 bar). The GCMD results show that the smectite mineral, hectorite, containing interlayer alkali and alkaline earth cations with relatively small ionic radii and high solvation and hydration energies (e.g., Li+, Na+ Mg2+, and Ca2+) does not intercalate dry CO2 and that the fully collapsed interlayer structure is the energetically most stable configuration. With increasing cation size and decreasing cation solvation energy, the energy barrier to CO2 intercalation decreases. With K+, Rb+, Cs+, Sr2+, and Ba2+ the monolayer structure is the stable configuration, and CO2 should spontaneously enter the interlayer. With Cs+ there is not even an energy barrier for CO2 intercalation, in agreement with the experimental XRD and NMR results that show clay layer expansion and CO2 incorporation. The number of intercalated CO2 molecules decreases with increasing size of the alkali cation but does not vary with ion size for the alkaline earth cations. 13C NMR spectroscopy and the GCMD simulations show that the average orientation of the intercalated CO2 molecules is with their O-C-O axes parallel to the basal clay surface and that they undergo a combination of rapid rotation about an axis perpendicular to the main molecular axis and wobbling motion with respect to the basal surface. Incorporation of CO2 in the interlayer decreases the coordination of Cs+ by the oxygen atoms of the basal surfaces, which is compensated by CO2 molecules entering their solvation shell, as predicted based on previously published NMR results. The GCMD simulations show that the strength of the interaction between the exchangeable cation and the clay structure dominates the intercalation energetics in dry scCO2. With relatively small cations, the cation-clay interactions outcompete cation solvation by CO2 molecules. The computed residence times for coordination among of interlayer species are consistent with the computed energetics.