Free fluoride levels above the WHO guideline maximum value of 1.5 mg/l have been reported in several parts of Malawi. Dental fluorosis has also been observed in the same areas such that search for local defluoridation techniques has become important in the country. The present research intended to determine the potential of using Malawi gypsum in defluoridation, identify the best pre-treatment of the gypsum and optimum conditions under which effective water defluoridation with the gypsum may be obtained. Laboratory experiments were carried out to explore defluoridation of drinking water using locally sourced gypsum and gypsum calcined at high temperatures. A 400 °C calcined phase of gypsum gave the highest defluoridation capacity of 67.80% compared to raw (uncalcined) gypsum, 200, 300 and 500 °C calcined phases. Powder X-ray diffraction (PXRD) pattern of the 400 °C phase revealed existence of less crystalline CaSO4 that was thought to be responsible for such relatively high defluoridation capacity. The dependence of the fluoride removal by the 400 °C calcined phase on other drinking water quality parameters was assessed by simple correlation analysis. Reaction kinetics and mechanisms of fluoride removal by the materials were also investigated. It was found that ion exchange was the dominant mechanism through which fluoride was removed from water by the materials.