The crystal chemistry of syngenite K2Ca(SO4)2·H2O and its lattice dynamics under low and high temperatures and high pressure were studied. The research facilities used include in situ temperature variable single-crystal (SCXRD) and powder X-ray diffraction (PXRD), in situ PXRD under high pressure (HP), thermal analysis (DSC and TGA), and Raman spectroscopy. For the first time, a detailed study of syngenite in the range of negative temperatures down to −180 °C was performed. It indicates the absence of phase transitions in the range from −180 °C to 240 °C. The largest expansion of the structure is observed along the α11, which is consistent with the layered architecture. The minor thermal expansion along the α22 is observed in the plane of the [Ca(SO4)2]2− layer, formed by the bassanite-type chains. The study of powder samples at HP up to 20 GPa was carried out using synchrotron radiation and a diamond anvil cell. The phase transition is registered at 10 GPa. After the decompression, the syngenite post-phase becomes partially amorphized.