This paper proposes a robust optimal attitude control design for multiple-input, multiple-output (MIMO) uncertain hexarotor micro aerial vehicles (MAVs) in the presence of parametric uncertainties, external time-varying disturbances, nonlinear dynamics, and coupling. The parametric uncertainties, external time-varying disturbances, nonlinear dynamics, and coupling are treated as the total disturbance in the proposed design. The proposed controller is achieved in two simple steps. First, an optimal linear-quadratic regulator (LQR) controller is designed to guarantee that the nominal closed-loop system is asymptotically stable without considering the total disturbance. After that, a disturbance observer is integrated into the closed-loop system to estimate the total disturbance acting on the system. The total disturbance is compensated by a compensation input based on the estimated total disturbance. Robust properties analysis is given to prove that the state is ultimately bounded in specified boundaries. Simulation results illustrate the robustness of the disturbance observer-based optimal attitude control design for hovering and aggressive flight missions in the presence of the total disturbance.