Benzopyran-annulated thiopyrano[2,3-b]thiochromen-5(4H)-ones have been synthesized by the domino Knoevenagel-hetero-Diels-Alder (DKHDA) reaction of 4-hydroxydithiocoumarin with O-allylated salicylaldehyde and O-propargylated salicylaldehyde in aqueous medium. The reaction requires only a single step operation and is highly regio- and stereoselective providing potentially bioactive polycyclic heterocycles in high yields.