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This paper is concerned with designing robust observer-based controller for continuous-time time-delay systems with saturating actuators and subject to time-varying uncertainties. With the assumption that the system states are not available but detectable, the observer-based output feedback controller is designed under some delay-dependent conditions derived, and the controller thus designed guarantees that the system without perturbations on its input matrices can be stabilized together with the domain of attraction. In addition, an iterative optimization algorithm is developed to acquire a maximal estimate of the domain of attraction. Moreover, in the presence of perturbations on the system input matrices, the gain of the observer given by the above-mentioned controller design rules is adjusted in terms of some stabilization conditions derived. The theoretical findings are finally verified by an illustrative example along with computer simulations.