The search for simple, earth-abundant, cheap, and nontoxic metal catalysts able to perform industrial hydrogenations is a topic of interest, transversal to many catalytic processes. Here, we show that isolated Fe-III-O sites on solids are able to dissociate and chemoselectively transfer H-2 to acetylene in an industrial process. For that, a novel, robust, and highly crystalline metal-organic framework (MOF), embedding Fe-III-OH2 single sites within its pores, was prepared in multigram scale and used as an efficient catalyst for the hydrogenation of 1% acetylene in ethylene streams under front-end conditions. Cutting-edge X-ray crystallography allowed the resolution of the crystal structure and snapshotted the single-atom nature of the catalytic Fe-III-O site. Translation of the active site concept to even more robust and inexpensive titania and zirconia supports enabled the industrially relevant hydrogenation of acetylene with similar activity to the Pd-catalyzed process.