This paper proposes an advanced diagonal decoupling control method for powered wheelchair systems. This control method is based on a combination of the systematic diagonalization technique and the neural network control design. As such, this control method reduces coupling effects on a multivariable system, leading to independent control design procedures. Using an obtained dynamic model, the problem of the plant's Jacobian calculation is eliminated in a neural network control design. The effectiveness of the proposed control method is verified in a real-time implementation on a powered wheelchair system. The obtained results confirm that robustness and desired performance of the overall system are guaranteed, even under parameter uncertainty effects.