The wettability of reservoir rocks is considered to be closely related to fluid distribution and CO2 geo-storage (CGS) security after injecting CO2 into reservoir. To investigate the influence of supercritical CO2 (ScCO2) injection on water wettability of shale, a sessile drop method was used to measure water contact angles of shale samples collected from Sichuan Basin (marine) and Ordos Basin (continental) at different ScCO2 exposure time and pressure. In addition, X-ray diffraction (XRD) and low-pressure N2 adsorption (LP-NA) were performed to evaluate the variations of mineral compositions and pore structure of shale. Results indicate that shale-water contact angles generally increased (from 22.74% to 43.94%) after ScCO2 exposure, which is primarily caused by the decrease of clay minerals and carbonates in shale. The water wettability of shale weakened after ScCO2 exposure, indicating that the interaction force between shale and water molecules changed, which may have reduced the resistance of water to flow in pores and fractures of shale, inferring that the alterations of shale water wettability after ScCO2 injection is beneficial to gas seepage in pore channels, but may exert a negative influence on CGS stability. This study provides a theoretical reference for CO2 sequestration and CO2-enhanced shale gas recovery (CS-ESGR).