The fascinating feature of metal–organic frameworks is that they can respond to external stimuli, unlike other inorganic materials. This feature corresponds to the framework’s flexibility, which originates with the long-range crystalline order of the framework accompanied by cooperative structural transformability. We have synthesized a novel metal–organic framework comprised of Cu(I) nodes with pyrazine linkers and benzene-1,3,5-tricarboxylate acting as template anions, named CUCAM-1 [Cu(Py)2(BTC)]n. In the presence of polar solvent systems, CUCAM-1 undergoes an irreversible structural transformation to yield a mixed phase that consists of HKUST-1 [Cu3(BTC)2(H2O)3]n and another CUCAM-2 [Cu(Py)(BTC)]n MOFs, whose novel structure is successfully revealed by continuous rotation electron diffraction from the mixture. In this structural transformation, a new ligand exchange occurs where template anions become ligands, confirmed by single crystal X-ray analysis. Further, structural transformation and the mechanism are explained by ab initio molecular dynamics (AIMD) simulations. Interestingly, different halides (F–, Cl–, and Br–) can be accompanied to affect/control the composition of the second phase by favoring the formation of the HKUST-1 phase over CUCAM-2, which was evident by the powder X-ray diffraction studies. Furthermore, the structural transformation induced by I– resulted in a colorimetric response due to the formation of a new MOF CUCAM-3, paving the way for use as an iodide detector.