Precise control of piezoelectric actuators used in micropositioning applications is strongly under the effect of internal and external disturbances. Undesired external forces, unmodelled dynamics, parameter uncertainties, time variation of parameters and hysteresis are some sources of disturbances. These effects not only degrade the performance efficiency, but also may lead to closed-loop instability. Several works have investigated the positioning accuracy for constant and slow time-varying disturbances. The main concern is controlling performance and also the presence of time-varying perturbations. Considering unknown source and magnitude of disturbances, the estimation of the existing disturbances would be inevitable. In this paper, a compound disturbance observer-based robust control is developed to achieve precise positioning in the presence of time-varying disturbances. In addition, a modified disturbance observer is proposed to remedy the effect of switching behaviour in the case of slow time variations. A modified Prandtl–Ishlinskii (PI) operator and its inverse are utilized for both identification and real-time compensation of the hysteresis effect. Experimental results depict that the proposed approach achieves precise micropositioning in the presence of estimated disturbances.