Abstract: To accurately identify unstable slopes in open-pit mines and analyze the influence mechanisms of rainfall infiltration on slope stability, this study focuses on a southern open-pit mine, integrating remote sensing monitoring and numerical simulation technologies to investigate slope deformation response patterns under the coupling effect of rainfall-infiltration-mechanics. Utilizing the small baseline subset interferometric synthetic aperture radar (SBAS-InSAR), multitemporal radar images from August 2017 to November 2019 were processed to generate vertical deformation rate distribution maps and spatiotemporal evolution diagrams, combined with meteorological data to statistically analyze settlement differences between rainy and dry seasons at key monitoring points. A Comsol-based hydro-mechanical coupling model was developed to simulate pore water pressure, effective saturation, and plastic strain field evolution during rainfall infiltration. Additionally, migration patterns of wetting fronts were extracted, and the model accuracy was validated by assessing the impact of shear strength degradation on stability. Monitoring results reveal significant subsidence is concentrated in the southeastern slope, with a maximum rate of −177 mm/year, and the rainy-season settlement at key points is 3.9 times that in dry-season. Uplift was observed in the northwestern slope and pit bottom, with a maximum rate of 70 mm/year. Numerical simulations demonstrate that rainfall infiltration increases shallow pore water pressure by up to 120 kPa, driving wetting fronts depths of the two measured profiles to reach 1.6 and 1.8 m respectively under the action of rainfall. Effective saturation in shallow soil surged by 35% during rainfall, while deep layers exhibited a trend of decreasing first and then increasing due to moisture migration hysteresis. Shear strength decreased by 14%–22%, and plastic yield zones expanded to the mid-slope when the safety factor dropped to 1.412. Simulated displacements showed 89% correlation with InSAR-measured subsidence. The subsidence in the southeastern part of the mining area is mainly dominated by the progressive creep deformation triggered by rainfall. During the rainy season, the infiltration of rainwater leads to a significant increase in the effective saturation and pore water pressure of the shallow rock and soil, resulting in a decrease in shear strength and the formation of a highly plastic strain zone and coupled with the effect of gravity, it drives the slope to slide along the weak plane.