Taking Nanfen open-pit iron mine in Liaoning Province as the engineering background, this study analyzes the effect of water-rock circulation on the mechanical properties of rock through a combination of macro-mechanical experiments and microstructure tests in the laboratory. Uniaxial compression experiments and acoustic wave tests are used to determine the degradation law of the mechanical properties of chlorite under the periodic action of water. The experimental results show that dry-wet cycles have a continuous and gradual effect on the rock sampled: Its uniaxial compressive strength, elastic modulus, and acoustic velocity all decrease gradually with an increase in the number of cycles. After 15 wet-dry cycles, the uniaxial compressive strength and elastic modulus of the rock decreased by 34.21% and 44.63%, respectively. Electron microscope scans of the rock indicate that the particle size, characteristics, and pore distribution at the rock surface had changed significantly after water-rock interaction. Finally, a drainage system and sliding force monitoring devices have been arranged at the mine site that can effectively reduce the impact of water-rock interaction on the stability of the mine. This combination of macro-experiments and micro-analysis allowed the weakening effect of dry-wet cycles on slope rock to be studied quantitatively, providing a theoretical reference for stability evaluation in geotechnical engineering.