Electro-mechanical brake (EMB) systems have garnered significant attention due to their distributed architecture. However, their signals from the brake pedal to the wheel-end actuators (WEAs) are transmitted electrically, meaning that any fault in EMB systems can severely impair the braking performance of vehicles. Consequently, the functional safety issues of EMB systems are the primary limitation of their widespread adoption. In response, this study first introduced the typical architectures of EMB and evaluated the automotive safety integrity level (ASIL) that must be achieved. Based on this, an EMB system architecture that satisfies functional safety standards was proposed. To accurately analyze the main factors affecting the probabilistic metric for hardware failures (PMHF) of the architecture, the failure rate of WEAs is further discussed. Specifically, a Markov chain was employed to define the operating states of the WEA matrix. The availability of each operating state was assessed based on the fault-tolerant control strategy. Finally, the failure rates of critical EMB parts, particularly the WEA matrix, were calculated. The results indicate that the unavailability of the WEA matrix is 9.244 × 10−3 FIT. Furthermore, the PMHFs of the EMB system for each safety goal are 6.14 FIT, 5.89 FIT, and 6.03 FIT, respectively, satisfying the ASIL-D requirements.