Magnetorheological (MR) fluid is a widely used smart material due to its outstanding properties. This paper presents the design, development, modeling, and prototype testing of a self-energizing and self-powered MR brake-by-wire system, whose aforementioned capabilities are enabled by brake energy harvesting. The system is composed mainly of a typical T-shaped drum-type MR brake and a wedge mechanism for self-energizing purpose. Into the system, we also install a generator that harvests regenerative energy during braking, thereby creating a self-power capability that cannot be found in common vehicular brake-by-wire systems. Brake torque analysis is conducted, and the braking process is simulated in a MATLAB/Simulink environment. Finite element analysis of the magnetic field, temperature field, and mechanical strength of critical components is carried out. The simulation results are used to optimize design parameters and material selection. Finally, prototypes and a corresponding test rig are established. The experimental results show that only about 30W of power is required to generate a 315 N.m brake torque and that the regenerative power produced by the generator can be used for braking, thus fulfilling the self-power requirement. The investigation of different wedge angles indicates that considerable self-energizing occurs under a small wedge angle. The findings demonstrate that the brake actuator, which has a relatively small volume, can significantly enlarge brake torque while harvesting brake energy. This feature enables the promising application of MR fluids in automotive brake systems.