This study evaluated the fermentative potential of eight industrial strains of Saccharomyces cerevisiae for producing mead from honeys originating from the Caatinga Biome in the semi-arid region of Pernambuco, Brazil. The fermentations revealed preferential consumption of glucose and fructose, with limited utilization of apparent sucrose. Despite presenting similar ethanol yields (38% mass conversion), the strains differed in fermentation rate, residual sugar profile, and metabolic composition of the final products. Strains TR313 and JP1 were selected for more detailed analyses, with JP1 standing out for its higher volumetric productivity (0.23 g·L⁻¹·h⁻¹) and shorter fermentation time. The mead produced by JP1 exhibited a higher content of amino acids, particularly alanine and proline, as well as bioactive compounds such as dehydroascorbic acid, glycerate, and GABA, which may confer antioxidant and nutraceutical properties. Analysis of volatile compounds indicated a predominance of 2-phenylethanol and tyrosol, with floral and fruity notes intensified by the presence of anisic acids and alcohols. Technological tests demonstrated that increasing biomass, supplementing with nitrogen, or cell immobilization accelerates fermentation without compromising yield. Thus, the JP1 strain shows promise as a ferment for producing regionally identified mead, combining autochthonous yeasts and honeys typical of the Caatinga biome, which can add socioeconomic value to beekeeping in the semi-arid Northeast of Brazil.