Water-rock interaction triggered by drilling and fracturing fluid retention in shale gas reservoirs induces secondary processes and the subsequent alteration of rock physical properties, critically modulating reservoir productivity. In this study, X-ray diffraction, nanoindentation, focused ion beam-scanning electron microscopy, and micro-computed tomography were utilized to characterize and analyze the mineral alteration, mechanical weakening and pore-fracture evolution of marine shale in the Longmaxi Formation, Sichuan Basin. The results reveal that the water-rock interaction preferentially dissolves clay minerals (mainly illite), feldspars and pyrite via hydration and redox reactions while promoting quartz and carbonate mineral recrystallization. The hydration-dissolution precipitation process significantly weakens the rock mass by reducing cohesion and the friction angle. This mechanical degradation is evidenced by a substantial decrease in elastic modulus, exhibiting pronounced anisotropy relative to stratifications. The resultant hetero-geneous stress fields initiate and propagate secondary pores and fractures, dramatically increasing the number, volume and surface area of pores. These newly formed structures integrate with pre-existing pore-fracture networks, markedly elevating overall porosity and enhancing interconnectivity, which consequently amplifies permeability by orders of magnitude. Additionally, water preferentially enters the reservoir through stratification, and the associated difference in water-rock interaction strength further enhances the heterogeneity of structural and mechanical heterogeneity. These findings link micro-scale physical-chemical reactions with the meso-scale mechanical properties and macro-scale pore-fracture structures, emphasize the key role of water-rock interaction in reshaping reservoir characteristics, and provide important insights for optimizing hydraulic fracturing strategies and improving shale gas recovery. Document Type: Original article Cited as: Mu, Y., Zou, C., Hu, Z., Duan, X., Guo, Q., Jing, Z. Impacts of multi-scale water-rock interaction on mineral alteration, mechanical weakening and pore-fracture evolution in marine shales. Advances in Geo-Energy Research, 2025, 17(1): 68-81. https://doi.org/10.46690/ager.2025.07.06