Here we present ecophysiological studies of the anaerobic sulfide oxidizers considered critical to cryptic sulfur cycling in oceanic oxygen minimum zones (OMZs). We find that HS− oxidation rates by microorganisms in the Chilean OMZ offshore from Dichato are sufficiently rapid (18 nM h−1), even at HS− concentrations well below 100 nM, to oxidize all sulfide produced during sulfate reduction in OMZs. Even at 100 nM, HS− is well below published half-saturation concentrations and we conclude that the sulfide-oxidizing bacteria in OMZs (likely the SUP05/ARTIC96BD lineage of the gammaproteobacteria) have high-affinity (>105 g−1 wet cells h−1) sulfur uptake systems. These specific affinities for sulfide are higher than those recorded for any other organism on any other substrate. Such high affinities likely allow anaerobic sulfide oxidizers to maintain vanishingly low sulfide concentrations in OMZs driving marine cryptic sulfur cycling. If more broadly distributed, such high-affinity sulfur biochemistry could facilitate sulfide-based metabolisms and prominent S-cycles in many other ostensibly sulfide-free environments.