Wettability plays a vital role in evaluating the structural integrity of caprock, typically shale, during the implementation of geological carbon storage (GCS). There have been limited investigations of the wettability of clay minerals, which is common in shale formations, especially concerning carbon dioxide (CO2) injection into saline aquifers. Furthermore, the consequence of CO2 dissolution in aquifer brine, resulting in acidic conditions, on the wettability of clay-CO2-brine systems has not been thoroughly investigated. This study utilizes molecular dynamic modeling to investigate the wettability of the illite-CO2-brine system under conditions corresponding to a typical deep saline aquifer. The wettability has been studied through the measurement of the water contact angle, adopting the microscopic wetting technique. In addition, the wettability has been further examined qualitatively by the analysis of relative concentration and radial distribution function. A comparative analysis was also carried out to assess the findings of this study in relation to applicable literature data. The results of this study suggested that illite�s wettability shifts from hydrophilic to hydrophobic under induced acidic conditions, irrespective of the brine�s salinity and the type of CO2 injection (either supercritical or subcritical). The water contact angle increased considerably from 44° in nonacidic conditions at 5 MPa and 333 K to 80° in acidic conditions at 10 MPa and 333 K. Furthermore, the competitive microscopic distribution revealed that acidic conditions facilitate the adsorption of CO2 onto illite. The results also showed that acidic conditions have a greater impact on the wettability alteration under supercritical conditions as opposed to subcritical conditions. In addition to the acidic conditions, the water wettability of the illite-CO2-brine system is significantly reduced by elevated pressure, increased brine salinity, and a higher level of organic content in the rock. This work is expected to contribute to a better understanding of the wettability characteristics of caprocks in various geo-storage scenarios. © 2024 American Chemical Society.