This article proposes a novel open-circuit switch fault diagnosis method (FDM) for a three-level interleaved buck converter (TLIBC) in a hydrogen production system based on the water electrolysis process. The control algorithm is suitably modified to ensure the same hydrogen production despite the fault. The TLIBC enables the interfacing of the power source (i.e., low-carbon energy sources) and electrolyzer while driving the hydrogen production of the system in terms of current or voltage. On one hand, the TLIBC can guarantee a continuity of operation in case of power switch failures because of its interleaved architecture. On the other hand, the appearance of a power switch failure may lead to a loss of performance. Therefore, it is crucial to accurately locate the failure in the TLIBC and implement a fault-tolerant control strategy for performance purposes. The proposed FDM relies on the comparison of the shape of the input current and the pulse width modulation (PWM) gate signal of each power switch. Finally, an experimental test bench of the hydrogen production system is designed and realized to evaluate the performance of the developed FDM and fault-tolerant control strategy for TLIBC during post-fault operation. It is implemented with a real-time control based on a MicroLabBox dSPACE (dSPACE, Paderborn, Germany) platform combined with a TI C2000 microcontroller. The obtained simulation and experimental results demonstrate that the proposed FDM can detect open-circuit switch failures in one switching period and reconfigure the control law accordingly to ensure the same current is delivered before the failure.