<p>Consisting of natural histidine residues, polyhistidine (PHis) simulates functional proteins. Traditional approaches towards PHis require the protection of imidazole groups before monomer synthesis and polymerization to prevent degradation and side reactions. In the contribution, histidine <i>N</i>-thiocarboxyanhydride (His-NTA) is directly synthesized in aqueous solution without protection. With the self-catalysis of the imidazole side group, the ring-closing reaction to form His-NTA does not require any activating reagent (<i>e.g.</i>, phosphorus tribromide), which is elucidated by density functional theory (DFT) calculations. His-NTA directly polymerizes into PHis bearing unprotected imidazole groups with designable molecular weights (4.2–7.7 kg/mol) and low dispersities (1.10–1.19). Kinetic experiments and Monte Carlo simulations reveal the elementary reactions and the relationship between the conversion of His-NTA and time during polymerization. Block copolymerization of His-NTA with sarcosine <i>N</i>-thiocarboxyanhydride (Sar-NTA) demonstrate versatile construction of functional polypept(o)ides. The triblock copoly(amino acid) PHis-<i>b</i>-PSar-<i>b</i>-PHis is capable to reversibly coordinate with transition metal ions (Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺) to form pH-sensitive hydrogels.</p>