The heterogeneous occurrence of coal-seam thickness represents a common geological characteristic in underground mining. Variations in coal thickness can directly alter the instability-failure behavior of coal–rock systems, thereby triggering various dynamic disasters. Therefore, revealing failure and disaster-inducing mechanisms of coal–rock systems dominated by coal-thickness effects is critical for deep mining engineering design as well as dynamic disaster prevention and control. To this end, uniaxial compression tests combined with acoustic emission (AE) monitoring were performed on coal–rock combinations with different coal thicknesses. The evolution laws of characteristic strengths (uniaxial compressive strength, initiation strength, and damage strength) versus coal thickness were systematically analyzed. Using full-process spatial localization of internal damage derived from absolute AE energy, an instability evolution model for coal–rock combinations was established. Furthermore, intrinsic disaster-inducing mechanisms governing coal–rock system instability under coal-thickness regulation were summarized, with corresponding engineering prevention-control suggestions put forward. The results show that: (1) UCS, initiation strength, and damage strength of specimens exhibit a nonlinear negative correlation with coal thickness. Initiation strength and damage strength account for approximately 50% and 75% of UCS, respectively; (2) Increasing coal thickness weakens the confinement effect of upper- and lower-sandstone, which shifts the dominant failure zone gradually from coal–rock interfaces to coal interiors. Meanwhile, internal energy accumulation-release processes of combinations present staged evolution characteristics; (3) Different coal thicknesses produce distinct disaster-evolution paths for coal–rock systems. Larger coal thickness corresponds to higher risks of high-energy dynamic disasters. Accordingly, a differentiated hierarchical prevention strategy of “thin protection, medium pressure relief, and thick control” was proposed. These findings provide a theoretical basis for mine engineering design and dynamic disaster prevention-control under dominant coal-thickness effects.