<p>CO₂ flooding is an essential method for the efficient development of low-permeability reservoirs. To investigate the mechanism of the CO₂–rock interaction and its influence on seepage capacity and oil displacement, cores with varied physical properties were selected. The experiments comprised CO₂ static immersion, dynamic dissolution, evaluation of phase seepage curves after displacement, and flow experiments on heterogeneous cores under different physical models. Physical alterations caused by the CO₂–rock interactions and their effects on seepage capacity were analyzed. Under different core scales, multiple rounds of CO₂ injection methods were studied, comparing gas channeling characteristics and oil recovery variations. The results indicate that prolonged reaction time elevates quartz and clay mineral content, gradually lowers solution pH, and increases Ca²⁺, Mg²⁺, Na⁺, and K⁺ concentrations. Moreover, the mass dissolution rate, porosity, and permeability of the core increase. Some micropores in the low-permeability core are plugged after displacement dissolution. CO₂ flooding increases bound water saturation, reduces residual oil saturation, expands the two-phase permeability zone, and enhances fluid seepage capacity. The displacement effect of parallel cores under different physical models is better than that of the three-dimensional model, and the oil recovery of the high-permeability layer significantly exceeds that of the low-permeability layer. Using multiple rounds of water–alternating–gas flooding can improve the fluidity of the flooding front while increasing the swept volume, reducing interfacial tension at the oil–water interface, and minimizing the occurrence of gas channeling, which is crucial for the efficient development of low-permeability reservoirs.</p>