This paper deals with the problem of fault detection for linear uncertain time-delay systems. The proposed method for Luenberger observers is developed for unknown input observers (UIOs), and a novel procedure for the design of residual based on UIOs is presented. The design procedure is carried out based on the model matching approach which minimizes the difference between generated residuals by the optimal observer and those by the designed observer in the presence of uncertainties. The optimal observer is designed for the ideal system and works so that the fault effect is maximized while the exogenous disturbances and noise effects are minimized. This observer can give disturbance decoupling in the presence of noise and uncertainties for linear uncertain time-delay systems. The developed method is applied to a numerical example, and the simulation results show that the proposed approach is able to detect faults reliably in the presence of modeling errors, disturbances, and noise.