Solvothermal reaction in N,N-dimethylformamide (DMF) between 1,6-bis(1-imidazolyl)-2,4-hexadiyne monohydrate (L1·H2O), isophthalic acid (H2L2), and Zn(NO3)2·6H2O gives the diacetylene-based mixed-ligand coordination polymer {[Zn(L1)(L2)](DMF)2}n (UMON-44) in 38% yield. Combination of DSC with variable-temperature single-crystal X-ray diffraction revealed the occurrence of two phase transitions spanning the ranges 129–144 K and 158–188 K. Furthermore, the three structurally similar phases of UMON-44 show giant negative and/or colossal positive thermal expansions. These unusual phenomena exist without any change in the contents of the unit cell. DFT calculations using the PBE+D3 dispersion scheme were able to distinguish between these polymorphs by accurately reproducing their salient structural features, although corrections in the size of the unit cell turned out to be necessary for the high-temperature phase to account for its large thermal expansion. In addition, the infrared spectra (vibration frequencies and peak intensities) of these theoretical models were calculated, allowing for univocal identification of the corresponding polymorphs. Last, the limits of our computational method were tested by calculating the phase transition temperatures and their associated enthalpies, and the derived figures compare favorably with the values determined experimentally.