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The forced-air self-aspirating flotation machine is the core equipment for achieving a horizontal configuration in a large-scale flotation circuit. During scale-up, power consumption increases significantly due to the requirement for a greater pulp suction volume, while flotation dynamics deteriorate. Therefore, it is difficult to meet the horizontal configuration requirement for a large-scale flotation process. In this study, the key factors influencing pulp suction capacity were analyzed, revealing that as impeller submergence depth increases, pulp suction capacity decreases sharply, while power consumption rises, which was determined to be the main limitation in scaling up a forced-air self-aspirating flotation machine. To address these challenges, a new design concept for large-scale forced-air self-aspirating flotation machines was developed, featuring an impeller–stator system positioned in the middle of a trough. This design eliminated the issue of the impeller moving farther from the overflow weir and prevented increasing pulp suction resistance during scale-up. Additionally, an independent design of the upper blades was introduced based on pulp suction demand, and the design method and scale-up equations for the new impeller were established. An industrial experiment system based on a 50 m³ forced-air self-aspirating flotation machine was established to verify the developed design schemes. The new impeller with a middle placement design achieved the best separation performance, exhibited low unit pulp suction power consumption, and demonstrated the most favorable overall performance. Using CFD simulations, the flow pattern and dynamic performance were calculated, including the pulp suction volume, circulation volume, and gas–liquid dispersion for large-scale forced-air self-aspirating flotation machines. The first and largest 160 m³ large-scale forced-air self-aspirating flotation cell was successfully developed and applied in a copper–sulfur mine, where the function of self-absorbing pulp was achieved and power consumption was effectively controlled. Finally, the feasibility and accuracy of the new large-scale forced-air self-aspirating flotation machine design and scale-up method were verified. In this paper, a large forced-air self-aspirating flotation machine is designed and developed which is capable of supporting horizontally configured large-scale flotation processes. This innovative approach significantly simplifies the processing layout and reduces both the equipment configuration complexity and energy consumption, offering a more efficient and cost-effective solution for large-scale mineral processing operations. Full article