Human operators in the transportation sector are exposed to whole-body vibration (WBV) while driving. Occupational exposure to WBV, predominant at low frequencies (<20 Hz), has been linked to spinal injuries and reduced functioning. This study aims at the design development of a novel semi-active seat suspension system featuring magneto-rheological elastomers (MREs) to mitigate the WBV. The proposed suspension system allows a greater range of strokes, while ensuring the MRE remains within an acceptable level of deformation. Several MRE samples were fabricated and characterized under shear mode. Afterward, a field- and frequency-dependent phenomenological model was developed to predict the viscoelastic properties of MREs as functions of both the excitation frequency and applied magnetic field. The MRE material model was subsequently used to design and optimize an adaptive seat suspension system incorporating a C-shaped MRE-based isolator in parallel and series with passive springs. The proposed adaptive seat suspension system demonstrated a frequency shift of 29% by increasing the applied current from 0 to 2 A. Finally, a 6-DOF lumped parameter model of a seated human subject combined with the proposed semi-active suspension system featuring the MRE isolator has been formulated to investigate the vibration transmissibility from the floor to the subject’s head.