A new hydrate of sulfadiazine calcium (Hydrate I) was discovered, and the crystal structure was determined using single crystal X-ray diffraction. Both channel-type water (9.23 wt %) and calcium-ion coordinated water (11.87 wt %) existed in the unit cell. The thermal stability and dehydration of Hydrate I were investigated by thermal gravimetric analysis, hot stage microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. A two-step dehydration process was detected from Hydrate I to anhydrous phase (AP) with the intermediate of the less-hydrated form (Hydrate II). The dehydration kinetics of Hydrate I with both channel-type and coordinated water was studied using model fitting method and model free method in isothermal mode. The dehydration activation energy was derived via the Friedman method. Further, the first-step dehydration of Hydrate I was determined to be the 2D phase boundary reaction mechanism, and the second-step dehydration was found to be...