Multi-layer co-production is a mainstream method for efficient development of coalbed methane (CBM) and coal series gas under multi-seam conditions. However, interlayer interferences during CBM co-production caused by differences in reservoir properties (especially permeability and pressure) between stacked CBM systems severely restrict the output of CBM from the production layers. The identification of interlayer interferences and optimization of production layer combinations are important scientific issues that need to be explored to achieve high CBM production. Physical simulation is an effective means of accomplishing this research objective. Physical simulations of CBM co-production were performed under designed permeability and pressure combinations based on self-developed experimental equipment, which is mainly composed of an injection subsystem, a vacuum subsystem, the model body subsystem, and a separation and metering subsystem. Coal samples were collected from three CBM basins in China to form a series of five permeability levels, specifically 0.2, 2, 10, 50, and 100 mD. We focused our analysis on the contribution of gas production from each production layer using the gas flow data obtained from the physical simulation experiments. The co-mining compatibility of the production layers is divided into four types based on the grading evaluation of gas contribution: Grade I, II, and III compatible, and incompatible, which represent gas production contribution of the weak seam ≥37.5%, 25%–37.5%, 12.5%–25%, and ≤12.5%, respectively. On this basis, a template for discriminating CBM co-production compatibility is constructed using the permeability ratio and pressure difference as basic parameters. The gas and water production data of representative CBM wells in the Bide-Santang basin were used to verify the reliability of the template, and the compatibility discrimination results show consistency with the production data. The average daily gas production per unit of coal thickness presents a decreasing trend with deteriorating compatibility of co-producing seams. Finally, an integrated technical process for the development of stacked CBM systems is proposed, including the hierarchical optimization of production layer combinations, identification of interlayer interferences and sources of produced water, and selection of suitable development methods and technology. We divided the production layer combinations into four types representing different development potentials based on the hierarchical method: most favorable, favorable, sub-favorable, and unfavorable. Suggestions are made for the key geological constraints (weak water-bearing reservoir, compatibility of CBM systems, shallow groundwater interference, and deep CBM condition) and specific development strategies for different types of production layer combinations. This study will enrich the geological understanding of CBM co-production and provide theoretical and technical support for the efficient development of stacked CBM systems.