An operationally simple and user-friendly new protocol for the synthesis of 3,5-disubstituted/annulated isothiazoles is devised utilizing β-ketodithioesters/β-ketothioamides and NH4OAc via C═O/C═S bond functionalization under metal- and catalyst-free conditions. The strategic [4 + 1] annulation initiated by NH4OAc is carbon-economic and relies on a sequential imine formation/cyclization/aerial oxidation cascade forming consecutive C-N and S-N bonds in one pot. A wide range of previously inaccessible and synthetically challenging isothiazoles are compatible with this transformation under nontoxic conditions with excellent functional group tolerance. The products bear useful synthetic handles for further functionalization.