In this article, a trajectory tracking control strategy is proposed for robot manipulators via a fully actuated system (FAS) approach, which has shown its simplicity and flexibility for most of the nonlinear controller design. However, the motion control for robot manipulators is more complicated since unknown dynamical model, external disturbances, friction forces, and various physical constraints are required to be considered. Therefore, the FAS approach cannot be straightforwardly applied. To address these challenges, the dynamic model of robot manipulators is established via model identification methods. Furthermore, based on the identified model, an FAS composite control strategy with simple structure is designed, which is achieved by integrating a high-order disturbance observer (HODO) in the inner loop, with an FAS trajectory tracking controller in the outer loop. Specifically, the HODO is utilized for handling the uncertain dynamics and external disturbances. Moreover, the controller gains are optimized using a gradient-based optimal parameter tuning method (OPTM). By imposing joint angle constraints, joint angular velocity constraints, and input torque limits into the formulation, the OPTM also ensures the satisfaction of these physical constraints. Numerical simulations and experiments are provided to validate the performance of the proposed controller.