Paroxetine HCl can exist as a nonstoichiometric hydrate (Form II) or as a stoichiometric hemihydrate (Form I); the latter is considered to be the stable form and its structure is well-known. However, little work has been performed to investigate its dehydration behavior; hence, the generation of the anhydrous form via dehydration of Form I was investigated. A combination of thermal (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)) and diffraction (variable-temperature X-ray powder diffraction (VT-XRPD)) techniques was used. Dehydrated Form I was prepared using ultradry conditions, and the resulting product was compared to dehydrated Form II. DSC indicated that the two dehydrated forms of Forms I and II had distinct melting points. TGA experiments allowed the calculation of the activation energy for the dehydration of Form I, which varies between 86 and 114 kJ/mol. Pawley refinement of the VT-XRPD data suggested that Form I dehydrates to an isostructural anhydrate, since the unit cell parameters of this new form were very similar to those of Form I with only a smaller volume as a consequence of dehydration. Comparison with dehydrated Form II indicated that these two forms represent different crystal entities; hence, a new anhydrous form of paroxetine HCl has been identified.