This paper studies the data-driven output-feedback fault-tolerant control (FTC) problem for unknown dynamic systems with faults changing system dynamics. In a framework of active FTC, two basic issues are addressed: the fault detection employing only the measured input-output information; the controller reconfiguration to achieve optimal output-feedback control in the presence of multiple faults. To detect faults and write the system state via the input-output data, an approach to data-driven design of a residual generator with a full-rank transformation matrix is presented. An output-feedback approximate dynamic programming method is developed to solve the optimal control problem under the condition that the unknown linear time-invariant discrete-time plant has multiple outputs. According to the above results and the proposed input-output data-based value function approximation structure of time-varying plants, a model-free output-feedback FTC scheme considering optimal performance is given. Finally, two numerical examples and a practical example of a DC motor control system are used to demonstrate the effectiveness of the proposed methods. (C) 2016 Elsevier Ltd. All rights reserved.