<p>In the milling process of the thin-walled workpiece, the layout of the fixture with multiple magnetorheology (MR) dampers plays a vital role for its directly effect to vibration depression which eventually influence its milling quality so that searching for a suitable layout to remarkably reduce the amplitude of milling vibration is essential which makes it imperative to construct an effective dynamic model to study their dynamic character for the fixture layout optimization. To cast off this predicament, it is the first time to construct a dynamic model of fixture-MR damper-workpiece system with generalized Lagrange equation by considering the coupling effect between the fixture and the workpiece, and its damping coefficient is obtained through the tension and compression tests. The model’s effectiveness is verified by comparing the workpiece’s velocity admittance through complex modal analysis and the one gets from the excitation experiment in different current. Then, this model is expanded for the fixture with multiple MR dampers and its layout optimized through related vibration shape and its applied current optimized as 2A with genetic algorithm (GA) in a given situation. Three experiments are designed to verify the layout’s effect with workpiece in different geometric size among the fixture with no dampers, with dampers in random locations and in optimized locations, and another experiment is designed to verify the significance of the current optimization with different current applied on the dampers. All the results in these experiments vividly show the significance and the effectiveness of this fixture layout optimization.</p>