The unprecedented use of a deep eutectic solvent (DES) for the ionothermal synthesis of Ca(II) based metal–organic frameworks (MOFs) has been explored. The 1 : 2 choline chloride : e-urea DES (e-urea = 2-imidazolidinone, ethylene urea) has been successfully employed for the preparation of Ca-MOFs with a series of dicarboxylic acid ligands. These materials have been structurally characterized by single-crystal and powder X-ray diffraction techniques as well as by thermo-gravimetric analysis and infrared, UV-visible and emission spectroscopy techniques in the crystalline state. The MOFs obtained have been found to be three-dimensional with the presence of channels occupied by coordinated e-urea solvent molecules. While the latter solvent acts as a bridging ligand in the case of terephthalate and isophthalate based MOFs, it behaves as a terminal ligand in the MOFs isolated with 2,5-dihydroxyterephthalate (dobdcH22−). With this ligand, two phases differing in the coordination mode of the dobdcH22− anion have been obtained. Interestingly, for one of them formulated as [Ca(dobdcH2)(e-urea)2], the crystals rapidly lost their transparency and luster upon exposure to air. This phenomenon could be rationalized by X-ray diffraction to result from the uptake of water molecules from the ambient atmosphere leading to the replacement of one e-urea molecule by H2O in the Ca(II) cation coordination sphere. These results demonstrate that the 1 : 2 choline chloride : e-urea DES can be considered as an effective solvent for the synthesis of water-sensitive Ca-MOFs.