Dehydration reaction of gypsum boards was investigated from both micro and macro levels, employing thermogravimetric analysis and a ventilated oven. A new dehydration mechanism of gypsum was proposed. The thermal properties of gypsum board such as enthalpy of reaction, specific heat capacity, and thermal conductivity were studied by differential scanning calorimetry and a heat transfer analyzer, respectively. The effect of void fraction and dehydration on thermal physical properties of gypsum board was investigated. The microstructure of the gypsum board at high temperature was studied with experiments and modeling. A model was proposed to describe the microstructure of a dehydrated system at high temperature, and experiments indicate its validity. Furthermore, the mechanical properties of gypsum at high temperature were investigated, and the effect of water content was discussed as well.