Abstract: The mechanism of SC-CO2–brine–rock interaction (SCBRI) and its effect on the mechanical properties of shale are crucial for shale oil development and CO2 sequestration. To clarify the influence of SCBRI on the micromechanics of shale, the lamina and matrix of shale were saturated with SC-CO2–brine for 2, 4, 6, and 8 days, respectively. The micro-scratch technique was then used to measure the localized fracture toughness before and after SC-CO2–brine saturation. Combining the micro-scratch results with SEM-QEMSCAN-EDS analysis, the differences in mineral composition and mechanical properties of lamina (primarily composed of carbonate minerals) and matrix (primarily composed of clay minerals) were studied. The QEMSCAN analysis and micro-scratch results indicate distinct mineralogical compositions and mechanical properties between the lamina and the matrix. The results showed that: (1) SCBRI leads to the decrease in carbonate mineral content and the significant increase in matrix porosity and laminar cracks. In addition, the damage degree increased at saturation for 6 days. (2) SCBRI weakens the mechanical properties of shale. The scratch depth of laminar and matrix increased by 34.38% and 1.02%, and the fracture toughness decreased by 34.38% and 13.11%. It showed a trend of first increasing and then decreasing. (3) SCBRI enhances the plastic deformation behavior of shale, and the plastic index of lamina and matrix increases by 18.75% and 21.58%, respectively. These results are of great significance for evaluating the mechanical properties of shale oil and gas extraction by CO2.