The aim of this study was to synthesize new thienobenzo-triazoles and to examine their inhibitory potency towards cholinesterases. The selectivity of their inhibition was also assessed, and the results were interpreted by molecular modeling. 15 new compounds have been successfully synthesized, differing in the substituent attached to the triazole ring or by the aromaticity of the central ring. A single compound 1 was synthesized by photocyclization route, while the alternative pathway gave a wide range of molecules of dihydro-thienobenzo-triazole and aromatized thienobenzo-triazole 2-15. Most of the new molecules showed better inhibitory potency towards butyrylcholinesterase (BChE). Computational studies suggest that thienobenzo-triazole and cholinesterases are linked via hydrogen bonds involving one of the triazole nitrogen, located between aromatic ligand residues and aromatic residues of the active cholinesterase sited. Alkyl interactions are also present. Molecular docking gives insight into the structure of the obtained complexes and the identification of stabilizing interactions between enzymes and a potential cholinesterase inhibitor. The newly synthesized thienobenzo-triazoles showed good characteristics for the future design of cholinesterase inhibitors and the search for therapeutics for the treatment of neurological disorders.