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The efficiency and safety of CO2 geological sequestration together with CO2-enhanced coalbed methane recovery (CO2-ECBM) depend on the dynamic evolution of coal–water–gas interfacial wettability under the influence of reservoir pressure, temperature, and the formation water chemistry. The wettability has a direct impact on the migration ability of CO2 into coal seams and the stability of the adsorption-sequestration and desorption efficiency of coalbed methane. Research has often overlooked the effect of in situ formation water on wettability, which may hinder accurate prediction of multiphase flow mechanisms in realistic environments. This study simulates in situ interactions among the CO2 formation water and coal for 25 days. Thus, it shows the wettability evolution in four stages. These stages are initial hydrophobicity, rapidly wetting, slowly wetting, and dynamic equilibrium. The formation water is acidic and multi-ionic in nature. This affects wettability through many mechanisms. These include mineral dissolution and precipitation, catalytic oxidation, and pore surface feedback. The impact of these mechanisms is greater than in low-salinity system. Moreover, this can bring about faster equilibration (20 days). The cause of equilibrium is the precipitation of secondary minerals (Fe(OH)3, amorphous SiO2, CaSO4), which self-limit reactions and smooth surface irregularities. The findings were used to propose a pressure regime in phases. These include low-pressure injection 0–5 days, medium- to high-pressure injection 5–10 days, gradual pressure reduction 10–20 days, and injection switch-off after 20 days for safe storage of CO2 in the long term. Overall, this study reveals the evolutionary pathway of coal wettability under reservoir conditions. Furthermore, it links the stage transitions to multiple mineral reactions, organic modifications, and pore-structure feedback. The kinetics derived present a basis for stage-wise pressure control concepts in CO2 storage and the CO2-ECBM process, which is experimentally anchored.