CyuA of Escherichia coli is an inducible desulfidase that degrades cysteine to pyruvate, ammonium, and hydrogen sulfide. Workers have conjectured that its role may be to defend bacteria against the toxic effects of cysteine. However, cyuA sits in an operon alongside cyuP, which encodes a cysteine importer that seems ill suited to protecting the cell from environmental cysteine. In this study, transport measurements established that CyuP is a cysteine-specific, high-flux importer. The concerted action of CyuP and CyuA allowed anaerobic E. coli to employ cysteine as either the sole nitrogen or the sole carbon/energy source. CyuA was essential for this function, and although other transporters can slowly bring cysteine into the cell, CyuP-proficient cells outcompeted cyuP mutants. Cells immediately consumed the ammonia and pyruvate that CyuA generated, with little or none escaping from the cell. The expression of the cyuPA operon depended upon both CyuR, a cysteine-activated transcriptional activator, and Crp. This control is consistent with its catabolic function. In fact, the cyuPA operon sits immediately downstream of the thrABCDEFG operon, which allows the analogous fermentation of serine and threonine; this arrangement suggests that this gene cluster may have moved jointly through the anaerobic biota, providing E. coli with the ability to ferment a limited set of amino acids. Interestingly, both the cyu- and thr-encoded pathways depend upon oxygen-sensitive enzymes and cannot contribute to amino acid catabolism in oxic environments. IMPORTANCE Cysteine is a singularly reactive amino acid; in high concentrations, it can disrupt cytoplasmic metabolism. This phenomenon prompted the view that the cyuPA operon of Escherichia coli serves to detoxify cysteine by degrading it. The present study indicates, however, that the natural purpose of that operon is to provide a concise route of cysteine fermentation. CyuP is the first dedicated cysteine importer to be functionally validated among the bacteria, and CyuA constitutes a cysteine desulfidase. Intriguingly, the CyuA iron-sulfur cofactor is inactivated by oxygen so that cysteine is, uniquely, a carbon source that is usable only in anoxic environments. Presumably, this constraint is tolerable because cysteine is scarce in oxic habitats. It also avoids sulfide release, which could interfere with aerobic respiration. Cysteine joins just serine and threonine as amino acids that E. coli is known to ferment, underscoring that this facultative bacterium is oriented toward the fermentation of carbohydrates.