The stability of the left-bank slope is a crucial geological engineering problem at the Baihetan hydropower station, China. Due to continuous excavations on the rock slope, different regions of the surrounding rock mass undergo varying degrees of unloading deformation. It is important to assess the stability of the rock slope from a macroscopic viewpoint by investigating its deformation characteristics and mechanisms. Therefore, in this work, microseismic (MS) monitoring was first employed to detect the progressive rock mass damage in the rock slope subjected to excavation, including the initiation, propagation, coalescence, and interaction of rock microfractures. Numerical modeling was subsequently performed to understand the deformation and failure mechanism of the rock slope. Moreover, traditional surveying approaches (i.e., multiple-point extensometers and inclinometers) and field observations were also used to analyze the deformation and failure characteristics of the rock slope. The MS monitoring results showed that spatiotemporal regularities in the evolution of seismic source locations were indicators of deformation failure and potential sliding surfaces. MS event clustering can be used to delineate activated pre-existing geological structures (i.e., LS331 and LS337). The simulation results show that the deformation and failure characteristics of the rock slope are mainly controlled by pre-existing weak structural planes (i.e., the intraformational faulted zones LS3319, LS331, and LS337 and fault F17). These results agree well with the results of geological data and conventional monitoring data. Our study reveals that an integrated approach combining MS monitoring, numerical modeling, traditional surveying, and field observations leads to a better understanding of the behavior of the rock slope under the influence of excavation as well as greater control of the working faces, ensuring safety under complex geological and excavation conditions.