It is difficult to exploit low-permeability reservoirs, and CO2 flooding is an effective method to improve oil recovery from low permeability reservoirs. However, in the process of CO2 flooding, acidic fluids dissolved in formation water will react with rock to cause dissolution and precipitation, resulting in pores and precipitates, changing the evolution law of seepage channels, destroying formation integrity, and affecting the effect of CO2 oil displacement. The change in rock’s physical properties and the mass transfer law between CO2-water-rock are unclear. This paper considers the coupling effects of seepage, mechanics, and chemistry when CO2 is injected into the formation. The mass transfer model of CO2-water-rock in the geochemical reaction process is established on this basis. The physical properties of the reservoir after CO2 injection are quantitatively studied based on the microscopic mechanism of chemical reaction, and the migration law of solute in the reservoir rock during CO2 flooding under the coupling effects of multiple fields is clarified. The experimental results show that with the increase in reaction time, the initial dissolution reaction of formation rocks will be transformed into a precipitation reaction of calcite, magnesite, and clay minerals. The porosity and permeability of the rocks near the well first increase and then decrease. The far well end is still dominated by dissolution reactions, and the average values of formation porosity and permeability show an upward trend. Although the dissolution reaction of CO2-water-rock can improve the physical properties of reservoir rocks to a certain extent, the mutual transformation of the dissolution reaction and precipitation reaction further exacerbates the heterogeneity of formation pore structure, leading to the instability of CO2 migration, uneven displacement, and destruction of formation stability. The research results of this paper solve the problem of quantitative calculation of physical parameters under the coupling effect of multiple fields after CO2 injection into reservoirs and can predict the changes in formation physical properties, which can provide a certain theoretical basis for evaluating formation integrity and adjusting CO2 injection under the condition of CO2 flooding.