An efficient three-component thieno[2,3-b]indole formation method was developed under metal-free conditions. The cascade cyclization was enabled by acid-promoted annulation of indoles, ketones and sulfur powder, which enabled modular synthesis of 2-substituted and 3-substituted thieno[2,3-b]indoles with excellent regioselectivity and broad functional group tolerance. DMF solvent played an important role in the regioselectivity control.