Change regulation of the physical properties of fluid is key to accurately predicting multiphase fluid flow in the production wellbore of CO2 flooding reservoirs. Given the characteristics of significant changes in pressure, temperature, and CO2 content in the whole wellbore of production wells in CO2 flooding reservoirs, this paper systematically studied the change rules of volume factor, viscosity, density, and solubility of well fluid for pressure 5~30 MPa, temperature 20~120 °C, and CO2 content 10~90% through single degassing PVT experiments. According to the experimental results, the volume factor of crude oil increases first and then decreases with the pressure increase. At the bubble point pressure (20 MPa), the volume factor of crude oil can reach 1.89 at high temperatures. The volume factor can be increased from 1.28 to 1.44 at 8 MPa when the temperature increases from 20 °C to 120 °C. Under the bubble point pressure, the increase in pressure increases the solubility of CO2, and the viscosity of crude oil decreases rapidly. In contrast, above the saturation pressure, the increase in pressure increases the viscosity of crude oil. Under the freezing point temperature (24 °C), the viscosity of crude oil decreases sharply with increase in temperature. In contrast, above the freezing point temperature, the viscosity change of crude oil is not sensitive to temperature. The wellbore temperature has a significant impact on the density of the well fluid. At 5 MPa, the temperature increases from 20 °C to 120 °C, which can reduce the density of high CO2 crude oil from 0.93 g/cm3 to 0.86 g/cm3. The solubility of CO2 in crude oil is sensitive to pressure. When the pressure increases from 5 MPa to 15 MPa at 20 °C, the solubility increases by 36.56 cm3/cm3. The results of this paper support the multiphase fluid flow law prediction of CO2 flooding production wells with a high gas–liquid ratio.