Clean technologies, which utilize or generate clean energy rather than fossil fuel-based energy, are under intense development to aid in addressing climate change. Current water desalination technologies are a growing user of fossil fuelderived electricity. A recently developed technology, termed the desalination fuel cell (DFC), can address this issue by instead using hydrogen gas to drive both feedwater desalination and green electricity generation simultaneously in a single cell. The main bottleneck is the use of Pt-based catalysts, which leads to high device costs and catalyst surface poisoning due to chloride ions (Cl − ) present in the feedwater. We here propose and demonstrate the first use of non-platinum group metal (non-PGM) catalysts toward DFCs. We synthesized a Fe/N/C based catalyst which demonstrated effective and Cl − tolerant oxygen reduction reaction ex situ and while used as a DFC cathode. The synthesis temperature and the metal concentrations were optimized using rotating disk electrode measurements, with an onset potential of up to 0.84 V vs RHE, on par with that of commercial Pt/C catalysts in a Cl − environment. When using the optimized Fe/N/C catalyst as a cathode in a prototype DFC, open circuit voltage was significantly improved relative to Pt/C, and measured cell voltage and desalination performance versus current density were nearly equivalent. Overall, these results show that non-PGM catalysts maintain or improve cell performance while significantly reducing cell costs, improving greatly the outlook for this nascent technology.