In the process of integrating supercritical CO2 (ScCO2)-enhanced shale gas recovery and geological sequestration, the mechanical properties of shale can be impacted by ScCO2 under high-temperature and high-pressure conditions. This can affect wellbore stability, production efficiency, and the safety of sequestration. To address this issue, this study investigated the interactions between shale and three types of fluids: ScCO2, water, and a combination of ScCO2 and water. Experiments were conducted at high pressure (15 MPa and 45 MPa) and high temperature (100 °C). Changes in shale's mechanical properties before and after immersion were analyzed using uniaxial compression tests and acoustic emission monitoring. The main cation content, microstructure, and element minerals of shale's solution after immersion were also studied. The results show that immersion in ScCO2 and related fluids deteriorates shale's mechanical properties. Immersion in ScCO2 has the least effect on shale strength, followed by the change in shale strength caused by immersion in water, and shale strength is the lowest after immersion in a combination of water and ScCO2. ScCO2 imbibition promotes the occurrence of micro-cracks, while immersion in water makes shale's matrix loose, forming a pore network structure that is most significantly affected by a combination of water and ScCO2. For unsoaked and water-immersed shale samples, the acoustic emission events mainly occur during the unstable crack propagation stage, while the acoustic emission events in shale samples treated with ScCO2 are more dispersed. Compared with previous dynamic pressure immersion experiments, the strength of shale after static pressure immersion increases by 10–30 MPa. This study aims to provide a more comprehensive understanding of the alterations in the mechanical properties of shale when subjected to high temperature and high-pressure immersion conditions. The findings provide valuable data for shale gas extraction and carbon sequestration.