Abstract: Water-rock interaction is a crucial inducing factor for the damage and instability of surrounding rocks in deep underground engineering. Using the uniaxial compression test, digital image correlation technology, and microstructure test, this study investigated the changes in the mechanical properties, local damage, and microstructures of granulite subjected to long-term immersion in different solutions. The influence mechanisms of water-rock interaction on the mechanical properties and damage evolution were discussed. The results indicate that with increasing immersion time, both the elastic modulus and uniaxial compressive strength decrease nonlinearly, while the corresponding deterioration degrees increase nonlinearly. The deterioration of mechanical properties in mine water is more serious than that in distilled water; however, the difference can be neglected after soaking for 150 d. With the progress of axial loading, the strain field undergoes a process from homogenization to localization and to fracture. The development level of local damage rises gradually accompanied by a nonlinear increase in the damage severity factor and a rapid increase after the peak stress, and a fluctuant decrease in the damage localization factor and a constant decrease after the peak stress. Meanwhile, the water-rock interaction exerts a promoting effect on the development of local damage. The development level at the peak stress rises with the increase of immersion time, and the effect of mine water is more obvious. In addition, the water-sensitivity substances in granulite react with the solutions, resulting in the development of pores, the increase of pore sizes, and the fragmentation of microstructures. The microstructures in mine water are more visibly deteriorated.