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Based on field geological survey and unmanned aerial vehicle (UAV) photography, this paper studied the inherent causes, intrinsic mechanisms, and kinematic characteristics of a catastrophic landslide of dissolved and fractured rock slope in a mountainous area of Southwestern China. The discrete element method (DEM) model of representative volume element of fractured rock mass considering karst existence was developed with its micromechanical parameters calibrated from laboratory element tests. The coupled finite difference and discrete element methods (FDM-DEM) were then employed to simulate deformation and failure evolution and collapse development of the rock slope with both internal and externally triggering factors properly addressed. The kinematic characteristics of mobile collapse debris flow were analyzed, and the numerical simulation results were validated by laboratory physical model test. The results show that the internal causes were mainly manifested in slope structure, lithology combination, karst, and fracture development, among which the unfavorable interaction disintegrated rock masses. The primary external cause was the staged underground coal-mining operations underneath the collapsed body, which led to large cracks appearing at the back edges of the slope. The maximum velocity of mobile collapse debris was about 65 m/s with the maximum travel distance of more than 600 m. Numerical simulation results matched well with both field forensic investigation and laboratory physical model test results. The findings would help further understand the deformation and failure process of fractured rock slope subject to underground mining and provide technical reference for accurate assessment and proper mitigation of similar landslide disasters. [ABSTRACT FROM AUTHOR]