The present article demonstrates a superior catalytic performance of glycerol-enriched calcium oxide for biodiesel production than other calcium-based counterparts. The proficiency of glycerol-enriched calcium oxide in catalyzing the methanolysis of crude Jatropha curcas oil containing high free fatty acids content was systematically researched by examining the effects of glycerol dose, temperature, time, methanol-to-oil molar ratio and calcium oxide (CaO) amount on the process. Acid value of oil was lowered by 49 times and the maximum oil conversion of 96.1% was reported after the methanolysis reaction that indicated the improved performance of calcium oxide, after its treatment with glycerol, in accelerating biodiesel production from crude oil with very high free fatty acids amount. An interaction between the reaction variables, their influence on the methanolysis and optimum conditions affecting the process were moreover determined by means of the regression analysis (response surface methodology). The statistical analysis suggested that both CaO amount and mole ratio of methanol-to-oil had a significant impact on the current biodiesel production process.