Abstract: Given the characteristics of strong suddenness, great destructive power, and wide impact range of hard roof-type coal bursts, proactive pressure relief has become a crucial mitigation measure for coal mines in such areas. In complex multi-key stratum working faces, low-level coal-rock pressure relief is often limited in range, leading to poor effectiveness. To address these issues, an innovative technique of whole-layer pre-fracture for pressure relief in high-level key strata is introduced. The structural model and evolution process of the key strata under different pre-fracture blocks are analyzed, and the structural change mode of the high key strata from “voussoir beam” to “short voussoir beam” to “unstable structure” to “fracture layer” is proposed, and the method for determining the optimal pre-fracture spacing has been provided. In light of the complex geological conditions of the 2412 working face at a Coal Mine, and based on the theory of pre-fracture block size variation, appropriate pre-fracture blasting layers and spacing are selected to conduct whole-layer pre-fracture blasting in high-level key strata. Subsequently, a comparative analysis of support pressure, microseism, and roadway stress between the conventional mining area and the high-level whole-layer pressure relief area is conducted, verifying the pressure relief effect of the whole-layer pre-fracture blasting in high-level key strata. The research results show that pre-fracture blasting has a weakening effect on the high thick and hard rock layer. During the advancing of the working face, roadway stresses are effectively reduced, and both the dynamic load coefficient of the hydraulic supports and the proportion of weighting duration are decreased. This decreases the number of microseismic events above 2000 J in the high-position rock strata, and effectively reduces the impact risk of the roadway and working face. This study provides a valuable theoretical and practical foundation for proactive coal burst prevention under similar geological conditions, contributing significantly to the advancement of coal mine safety technology in China.