Hydrogen leaks are potentially dangerous faults in fuel cell systems that are fed with hydrogen-rich gas mixtures. This brief presents an approach to hydrogen leak detection and, thus, complements direct detection using hydrogen sensors. It relies on simple mass balance equations of an anode filling volume after taking into account the natural leak of the stack. A hydrogen mass flow, anode pressure, and relative humidity sensor are employed. Hydrogen leak detection without the use of relative humidity sensors is considered by employing adaptive alarm thresholds to eliminate false alarms. The validity of the method is also discussed in terms of common hydrogen supply system configurations. The detection method is validated using a 1.25-kW polymer electrolyte membrane fuel cell stack in a laboratory facility where leaks could be introduced in a controlled manner.