In this work, experiments and molecular dynamics (MD) simulations are carried out to explore the synergistic effect of supercritical CO2 (scCO2) and organic solvent on intercalation and exfoliation of graphene. Experimental characterizations via transmission electron microscopy, atomic force microscopy and Raman spectroscopy indicate that by combining scCO2 and organic solvent (N-methylpyrrolidone, NMP), few-layer graphene is successfully exfoliated from graphite, among which over 30% is 1-4 layers, and 55% is 5-8 layers. Systematic experiments have shown that compared with pure scCO2 or NMP, the mixed scCO2 and NMP can significantly increase the amount of graphene and the rate of few-layer graphene, and the optimum volume fraction of NMP is 25%. Parallel MD simulations indicate that the scCO2 molecules first diffuse into the interlayer of graphite, and then the larger NMP molecules insert as wedges and further expand interlayer spacing, promoting intercalation and exfoliation. The iteration of scCO2 diffusion and the NMP wedge can generate positive feedback to improve the exfoliation productivity and efficiency. This work explores the synergistic effect of scCO2 and NMP on the exfoliation of graphene, which may provide useful insights for exfoliation of other two dimensional materials. © 2019 the Owner Societies.