An isothiourea-catalysed asymmetric Michael/lactamization cascade reaction of 2-aminobenzothiophenes and α,β-unsaturated anhydrides was developed for the first time. In the presence of a 10 mol% isothiourea catalyst, various benzothienopyridinones were afforded in good to excellent yields (73–96%) with excellent enantioselectivities (up to 98 : 2 er).