Understanding the formation mechanism of bed separation in coal seam mining under a karst landform is needed for the prevention and control of roof-separated water damage in such areas. This research used a mine in the northern Guizhou coalfield, China, as a case study, and applied theoretical analysis, numerical simulation, and on-site measurement to develop a circular cave structure model in a key stratum. The dynamic evolution of a separation bed was analyzed from several aspects, including the formation mechanism, development location, the mechanical condition of local karst caves, fracture evolution, and fractal rules. Verification using in situ measurements is presented for the case study mine, and a quantitative evaluation method for water inrush from bed separation and improved fusion weighting is proposed based on a cloud model. The research results indicate the following: (1) Tensile cracks are prone to occur above and below a karst cave, which produce an impact of connectivity on the separated space. (2) When the working face advances to 270 m in coal mining, longitudinal tensile cracks below the karst cave gradually increase and the width of the bed separation crack shrinks to 68.2 m, with a maximum separation layer height of 3.01 m. (3) Based on the cloud model and the improved weighted fusion method, the risk of water inrush in bed separation is judged as “high”. The En of the cloud digital features is 0.0622 and the He is 0.0307, achieving a quantitative evaluation of water inrush in the separation layer that is consistent with on-site practice, and is highly stable and reliable. This study improves the understanding of the development pattern of bed separation and water inrush risk assessment in coal seam mining under a karst cave landform.