This investigation was carried out to highlight the influence of the variation of permeability of the porous media with respect to the injection orientations during enhanced gas recovery (EGR) by CO2 injection using different core samples of different petrophysical properties. The laboratory investigation was performed using core flooding technique at 1300 psig and 50 °C. The injection rates were expressed in terms of the interstitial velocities to give an indication of its magnitude and variation based on the petrophysical properties of each core sample tested. Bandera Grey, Grey Berea, and Buff Berea sandstone core samples were used with measured permeabilities of 16.08, 217.04, and 560.63 md, respectively. The dispersion coefficient was observed to increase with a decrease in permeability, with Bandera Grey having the highest dispersion coefficient and invariably higher mixing between the injected CO2 and the nascent CH4. Furthermore, this dispersion was more pronounced in the horizontal injection orientation compared to the vertical orientation with, again, the lowest permeability having a higher dispersion coefficient in the horizontal orientation by about 50%. This study highlights the importance of the permeability variation in the design of the injection strategy of EGR and provides a revision of the CO2 plume propagation at reservoir conditions during injection.