At present, it is necessary to change the development method to improve the development of gas reservoirs entering the middle to late stage of development. CCUS-EGR can drive out residual gas while burying carbon, which is an economically feasible method. For most reservoirs, water intrusion is severe or there is a large amount of pore water, so it is necessary to study the impact of CO2-water–rock reaction on reservoir physical properties and pore structure. Rock sample displacement experiments were implemented, CO2 were injected into carbonate rock samples and tight sandstones saturated with bound water for displacement, and the changes in the permeability of the rock samples during the displacement process were monitored. The pore structure of rock samples before and after CO2 water rock reaction was measured using nuclear magnetic resonance equipment, and the different water rock reaction occurring in different rock types were studied combined with XRD testing. This study provides a reference for on-site CO2 injection testing. For carbonate rock samples mainly com-posed of dolomite and calcite, supercritical CO2 has a negative effect on the permeability of the rock samples. Under the temperature and pressure conditions of the reservoir, CO2 dissolves in water to form carbonic acid. Carbonic acid reacts with CaCO3 to form HCO3−/CO32− ions, which dissolve in the solution. When the HCO3− ions in the solution become supersaturated, calcium carbonate precipitates. The micropores in carbonate rocks are expanded by acid dissolution, while the macropores are filled by precipitated calcium carbonate. After injecting CO2 for 1175 min, the porosity of the rock sample decreased by 10.44% and the reservoir permeability decreased by 54.8%. For dense sandstone rock samples mainly composed of feldspar and clay, supercritical CO2 has also a negative effect on the permeability of the rock samples. Under the temperature and pressure conditions of the reservoir, solid CaCO3 particles, solid SiO2 particles, and liquid SiO4 are directly generated in the CO2 water rock reaction, blocking micropores and reducing reservoir permeability. After injecting CO2 for 1175 min, the porosity decreased by 2.56% and the permeability decreased by 24.10%. In this study, CO2-water–rock reaction displacement experiments were conducted on carbonate rocks and tight sandstones, the CO2 water rock reaction mechanism of different lithology reservoirs were deeply studied combined with nuclear magnetic resonance and XRD experiments, and the influence of CO2-water–rock reaction on the pore space and permeability of different lithology reservoirs were finally obtained.