A fundamental requirement in robot control is the capability to improve the robot–environment interaction performance. Motivated by the fact that humans are able to adapt limb impedance to stably interact with various environments with skillful dexterity, this paper investigates the variable impedance control for robots, subject to uncertainties from plant model or environment. The proposed variable impedance control assists the robot to perform given interaction tasks with its unknown environment and improves the overall robot–environment system performance. The stiffness, damping, and inertia can be changed during interaction tasks, which results in configuration-dependent impedance dynamics. The uncertainty and disturbance estimator (UDE) is used to approximate the plant model with only partial information known. The prominent feature of the UDE-based control is that only the bandwidth information of the unknown plant model is needed for the control design. A stability condition for selecting the stiffness, damping, and inertia in the impedance model is provided to guarantee the stability of the control system. Extensive simulation studies are carried out to illustrate the effectiveness of the proposed method.