An experimental method has been developed to determine the wettability, i.e., the contact angle, of the crude oil−reservoir brine−reservoir rock system with dissolution of CO2 at high pressures and elevated temperatures, using the axisymmetric drop shape analysis (ADSA) technique for the sessile drop case. In the experiment, a see-through windowed high-pressure cell is prefilled with reservoir brine to submerge the reservoir rock. Subsequently, CO2 is slowly injected through the brine phase to pressurize the system to a prespecified pressure at a constant temperature. After the CO2−reservoir brine system reaches the equilibrium state, a crude oil sample is introduced by using a specially designed syringe delivery system to form a sessile oil drop on the reservoir rock inside the pressure cell. The sequential images of the dynamic sessile oil drop are acquired and analyzed by applying computer-aided image acquisition and processing techniques to measure the dynamic contact angles at different times. It is found that the dynamic contact angle between the crude oil and the reservoir rock in the presence of CO2-saturated reservoir brine remains almost constant at a given pressure and a constant temperature, though CO2 is gradually dissolved into the sessile oil drop until the latter is completely saturated with the former. It is also found that the equilibrium contact angle increases as the pressure increases, whereas it decreases as the temperature increases. In comparison with the equilibrium contact angle data for the crude oil−reservoir brine−reservoir rock system without any dissolution of CO2, the equilibrium contact angles of the crude oil−reservoir brine−reservoir rock system with dissolution of CO2 are smaller at T = 27 °C but larger at T = 58 °C. Such wettability alteration will significantly affect oil recovery and subsequent storage when CO2 is injected into an oil reservoir at high pressures.