The possibility of exploiting supramolecular architectures for the preparation of innovative mechano- chromic devices has been extended by designing novel thienyl-substituted 1,4- bis-(ethynyl)benzene dyes, which are characterized by a conjugated, rigid, rodlike core structure. This new family of chromophores was synthesized ac- cording to a simple two-step sequential cross-coupling reaction, and the optical properties were investigated in solution and in a polymeric matrix. To tune the mechanochromic performances in smart polymer materials, a virtual screening was set up that was able to select a derivative with optimal spectral features. The effective combination of experimental and computational inves- tigations allowed us to spot those ho- mologues with already potential aniso- tropic and aggregachromic features and characterized by the best spectral prop- erties and luminescent response. The best candidate was synthesized and dis- persed into a polyethylene matrix, indeed achieving an “in silico de- signed” mechanochromic material. Be- sides the specific applications of this novel material, the integration of com- putational and experimental techniques reported here defines an efficient pro- tocol that can be applied to make a se- lection among similar dye candidates, which constitute the essential respon- sive part of such supramolecular devices.