The effect of milling on the transitions of sulfathiazole polymorphs in the absence and presence of solvent and excipients was monitored by X-ray powder diffraction (XRPD), attenuated total reflectance infrared (ATR-IR), and near-infrared (NIR) spectroscopy. Sulfathiazole forms FII-FV undergo a transformation toward the metastable FI, which involves an intermediate amorphous stage upon milling at ambient temperature. Milling the commercial form (FC) with catalytic amounts of solvent converts it to pure FIV or to mixtures of FI and FIV depending on the solvent used. Pure FIV can be easily prepared from FC by this method. The physical stability of nonmechanically activated pure sulfathiazole forms in the presence of different levels of relative humidity (RH) was also investigated. At low RH, all sulfathiazole forms are kinetically stable, but at RH levels above 70% FII, FC and FIV remain stable, while FI and FV transform to mixtures of FII and FIV without any apparent change in the external form of the crystals. Comilling FC with a range of excipients gave results that depended on the excipient used, and comilling with cellulose gave samples that had an amorphous content that was stable at 10% RH for at least nine months at ambient temperature.