The high-pressure permeation and sorption behavior of supercritical carbon dioxide (sc-CO2) in glassy Matrimid® 5218 polymer membranes were extensively investigated. The effect of pressure (0–120 bar) and temperature (25–55 °C) was examined. The observations were related to the intrinsic membrane properties, plasticization phenomena and the CO2 fluid properties. The phase transition from gaseous (-like sc) CO2 to liquid (-like sc) CO2 has the largest influence on the CO2 fluid properties and therefore was found to have the most influence on the CO2 sorption and CO2 permeability. The CO2 sorption was directly dependent on the CO2 density in the liquid (-like sc) regime. The CO2 permeability of Matrimid® 5218 showed typical CO2-induced plasticization behavior in the gaseous (-like sc) CO2 regime. When entering the liquid (-like sc) CO2 regime, the extent of plasticization was found to be independent of the applied feed pressure in this regime. The membranes showed strong hysteresis with pressure. The permeation history of the membrane thus has a large influence on the time-dependent permeability behavior. Clearly, the CO2 permeability behavior at these high pressures in glassy Matrimid® 5218 is determined by a combination of the CO2 fluid density and plasticization phenomena.