Iron is the quintessential biometal supporting biological catalysis and life as we know it. Before dietary iron enters human circulation, it is transformed by the diverse species of the animal microbiome. Most of these species cannot make but nonetheless require iron in its heme form. Canonical pathways for breaking down and repurposing heme depend on O2, which is unavailable in the GI tract and several pathological microenvironments. We describe physiological, biochemical, and structural evidence for the anaerobic removal of iron from heme by HmuS, a >1400 amino acid, monomeric, an extraordinary microbial de-chelatase that deconstructs heme to produce PPIX and Fe(II). This enzyme and its associated pathway are pervasive in the GI tracts of humans, where they may serve as the primary entry point of heme-iron from the diet and recycled cells into the host-microbiome ecosystem.