CO2 miscible flooding is a prospective production method to enhance oil recovery (EOR), especially in low-permeability reservoirs. However, there is a lack of comprehensive and systematic understanding of the key parameters and dominant EOR mechanism of CO2 miscible flooding. In this work, the sensitivity of key parameters, such as oil viscosity, permeability, permeability ratio, and pressure, is analyzed by CO2 flooding physical simulation experiments. The adjuvants for CO2 miscible flooding of the Changqing crude oils are evaluated and optimized. The production performance of overpressure CO2 miscible flooding is studied by CO2 core flood test, and the oil micro-distribution before and after CO2 miscible flooding is characterized using nuclear magnetic resonance (NMR), and the micro EOR mechanism of CO2 miscible flooding is revealed. The results show that CO2 immiscible flooding is suitable for the development of low-viscosity crude oil (<50 mPa s), especially for oil viscosity of less than 10 mPa s. CO2 miscible flooding is advisable for low-permeability and medium and high-permeability reservoirs, especially for reservoir permeability of higher than 10 mD. Above the MMP, the oil recovery factor is over 85% and the increase rate slows down with pressure, CO2 miscible flooding is preferred for the high-pressure reservoir. CO2 miscible flooding is applicable for reservoirs with a permeability ratio of less than 2.5, especially for a permeability ratio of less than 2. Compared with 0.8 times MMP pure CO2 flooding, the time of gas channeling, and oil recovery for CO2 miscible flooding is delayed from 0.69 PV to 0.76 PV, and enhanced to 93.04% from 72.61%, respectively, with the help of adjuvants for CO2 miscible flooding, NP-9. The adjuvants for CO2 miscible flooding could effectively promote the realization of miscible flooding for CO2 and crude oils with an injection pressure of less than the MMP. CO2 has excellent oil displacement ability in low-permeability reservoirs, especially for miscible flooding, and the core oil saturation is obviously reduced. Overpressure CO2 miscible flooding could expand the swept volume and more efficiently displace oil in low-permeability reservoirs compared to an injection pressure of 1.0 times MMP. After overpressure CO2 miscible flooding, the residual oil in the low-permeability cores is distributed more evenly.