To effectively seal preferential breakthrough channels and to increase the sweep volume and flooding efficiency of carbon dioxide, in-situ experimental models with different permeabilities were established, including a heterogeneous core model, a high permeability zone gas-channeling model, and a fracture model. CO2 was measured at different stages of breakthrough time, channeling time, and degrees of recovery. On this basis, a high-strength, high-performance channeling sealing agent, ethylene diamine, containing formation water, starch, unsaturated monomer, a cross-linking agent, and a gel control agent was selected to carry out the carbon dioxide sealing control experiments in various permeability core models. The channeling sealing agent reacted with the carbon dioxide and formed carbamate. The experimental results showed that the carbon dioxide sweep volume was seriously affected by the gas channeling, and the gas channeling effect became stronger with increasing core heterogeneity. As the gas flooding effect weakened in the low-variation permeability conditions, the degree of recovery decreased with the increasing permeability. When the variation exceeded 100, the degree of recovery decreased rapidly and the gas channeling became severe. The low permeability reservoirs became difficult to reach, and as a result, the degree of recovery decreased. By using the high-strength, high-performance channeling sealing agent, ethylenediamine, the relatively high permeable channeling layers in the matrix were sealed in a stable manner and the carbon dioxide flooding sweep volume was expanded effectively. The in-situ degree of recovery increased by over 30%.