Molecular simulation techniques have revealed that the incorporation of fullerenes within porous aromatic frameworks (PAFs) remarkably enhances methanol uptake while inhibiting water uptake. The highest selectivity of methanol over water is found to be 1540 at low pressure (1 kPa) and decreases gradually with increasing pressure. The adsorption of water is very small compared to methanol, a useful material property for membrane and adsorbent-based separations. Grand canonical Monte Carlo (GCMC) simulations are utilized to calculate the pure component and mixture adsorption isotherms. The water and methanol mixture simulations show that water uptake is further inhibited above the pure component results because of the dominant methanol adsorption. Molecular dynamics (MD) simulations confirm that water diffusivity is also inhibited by strong methanol adsorption in the mixture. Overall, this study reveals profound hydrophobicity in C60@PAF materials and recommends C60@PAFs as suitable applicants for adsorbent and membrane-based separations of methanol/water mixtures and other alcohol/water separation applications.