For the first time, α-calcium sulfate hemihydrate (α-HH) was successfully prepared from calcium sulfate dihydrate (DH) in methanol–water solution under atmospheric pressure. The effect of methanol concentrations (40–73 mol%) on the transition from DH to α-HH were investigated at temperatures (60°–75°C) within a reaction time of 36 h. The results showed that an increase in methanol concentration could lower the transition temperature. The transition was speeded up by increasing methanol concentration from 47 to 57 mol% at 75°C. When the temperature dropped to 70°C, the transition rate firstly increased with the methanol concentration until it reached 69 mol% and then exhibited a reverse trend with increasing methanol concentration from 71 to 73 mol%. The accelerating effect, involved during the nucleation of α-HH, attributes to the elevated supersaturation due to the fall in the water activity resulting from the increasing methanol concentration. The retarding effect, involved during the crystal growth of α-HH, was likely derived from the specific adsorption of methanol molecules onto the surfaces of α-HH crystals. Overall, the aqueous solution of methanol could act as a novel category of medium suitable for the α-HH preparation from DH.