High contrast mechanochromic materials are prominent candidates for sensor, security and memory applications; however, the development of materials with a large luminescence change (Δλ em >100 nm) under external stimuli is challenging. Considering that polymorphic molecules usually exhibit reversible mechanochromism, polymorph prediction is adopted for the first time to guide the design of high-contrast mechanochromic materials in this study. We designed and synthesized a series of donor-π-acceptor pyran derivatives bearing different electron donors and acceptors as model systems. The polymorph prediction indicated that 4-dicyanomethylene-2,6-distyryl-4H-pyran and 4H-pyran-4-one derivatives had the potential to crystallize in both monomer and π-dimer aggregates, while barbituric acid-based compound tended to pack tightly in all aggregated states. The experimental results agreed well with the prediction that the derivatives potentially possessing both monomer and π-dimer aggregate structures exhibit excellent mechanochromic behavior, whereas the fluorescence difference for the barbituric acid-based compounds is minimal. Moreover, a compound with an excellent fluorescence difference of three colors during reversible mechanochromism was chosen as the candidate for an optical recording material and security ink. This work proposes an effective