2-Thiobenzazole is among the privileged heterocyclic scaffolds in medicinal chemistry. Constructing such structural components in DNA-encoded libraries (DELs) may promote related bioactive hit discovery in a high-throughput fashion. Herein, we reported a DNA-compatible mild-condition synthetic methodology to efficiently forge functionalized 2-thiobenzazole scaffolds, realizing on-DNA sulfhydryl incorporation with broad substrate scope, thereby expanding the scope of 2-thiobenzazole-focused DNA-encoded chemical libraries.