Solid-state density functional theory (DFT), molecular dynamics (MD), and terahertz (THz) spectroscopy were used to study the formation of enantiotropically related conformational Form I and Form II polymorphs of the pharmaceutical compound, probucol. DFT calculations were performed on the crystal systems to compare relative lattice energies and the solvent stabilization of the metastable Form II structure. The thermodynamics of solvent inclusion in the Form II-MeOH crystal system were determined from MD simulations, as was the favored conformation of molecular probucol in methanol and ethanol solutions. The findings from both solid-state DFT and MD calculations suggest that the preferred molecular orientations of the probucol molecule in solution and the probable inclusion of methanol in the crystal lattice during the crystallization process lead to the solvent selectivity of the probucol polymorph formation. The additional stabilization energy provided by the crystallization solvent facilitates the nucleation and growth of the Form II polymorph under conditions that favor this metastable crystal form over the thermodynamically stable Form I, despite the higher energy molecular and crystalline configurations of probucol Form II. We demonstrate the influence of solvent on the formation of pharmaceutical polymorphs and provide a molecular-level view of complex interactions leading to polymorphism using a combination of computational methods and THz spectral data.