A mild, catalyst and oxidant-free efficient protocol for synthesizing α-ketothioamides is reported with a broad substrate scope. The presented protocol demonstrates the confined reactivity of amines. The polysulfide derived from elemental sulfur and amines in an aqueous medium drives the pathway toward diverse α-ketothioamides over thioamides. Substrates with different substituent groups were compatible with the presented protocol, and the respective ketothioamides were separated in good to excellent yields. The ketothioamides, known to exhibit anti-cancer properties, were synthesized by the proposed protocol. Furthermore, the synthetic utility was explored with the typical synthesis of ketoamides.