Abstract: CO₂-enhanced coalbed methane recovery (CO₂-ECBM) is a key method for CO₂ geological utilization and sequestration. It holds promise for addressing challenges such as soft, low-permeability coal seams with difficult gas extraction, poor development performance, rapid production decline, and low recovery rates, as exemplified by the Huainan mining area. The geochemical interactions of CO₂ injection into coal seams and inorganic minerals in coal can alter the pore-fracture structure and permeability of the coal, significantly influencing CO₂ sequestration capacity and methane production enhancement. Therefore, considering the effects of effective stress, temperature, and geochemical interactions—including competitive adsorption, diffusion, seepage of CO₂ and CH₄, and CO₂-water-coal geochemical interactions, as well as their impact on the dynamic evolution of coal seam porosity and permeability—a fully coupled Thermo-Hydro-Mechanical-Chemical mathematical model was developed for the seepage-stress-temperature-chemical interactions in CO₂-injected coal reservoirs. Numerical simulation studies on CO₂-ECBM were conducted for the Huainan coalfield to analyze the effect of geochemical interactions on CH₄ production enhancement during CO₂ injection, as well as the influence of injection pressure, initial permeability, and water saturation on CH₄ production and CO₂ sequestration. The results showed a high degree of consistency between the mathematical model and experimental outcomes, with the average error range for CH₄ and CO₂ mixture volumetric fractions and production rates falling within 1%−10%. Compared to scenarios ignoring CO₂-water-coal geochemical interactions, the cumulative CH₄ production decreased by 11%, while cumulative CO₂ storage increased by 19.8%, indicating that neglecting geochemical interactions could lead to an overestimation of CH₄ production and underestimation of CO₂ storage capacity. Higher injection pressures and initial permeability of coal reservoirs resulted in more significant CH₄ production enhancement and CO₂ sequestration, whereas high water saturation adversely affected both processes. These findings suggest that CO₂-ECBM should be tailored to reservoir properties, optimizing target layers and injection strategies to maximize CH₄ production and CO₂ storage. Geochemical interactions were found to alleviate the reservoir pressure increase caused by CO₂ injection, reduce the free-state CO₂ content in fractures. This, in turn, mitigated permeability decline due to stress-strain effects, promoting permeability recovery by 2.4%−3.3%. The permeability recovery further facilitated pressure transmission, CO₂ adsorption, and CH₄ desorption/diffusion, ultimately enhancing CH₄ production and CO₂ sequestration efficiency.