Craft beer quality is the result of the complex interactions among ingredients. The purpose of this work was to assess the influence of combinations of cereal mixtures, yeast strains, and sucrose added for the refermentation in bottle on the physico-chemical and sensory characteristics of the resulting beers in order to maximize their antioxidant content and overall quality. More in depth, brewing trials were carried out with 16 combinations of 2 cereal mixtures (made of 60% malted barley/40% unmalted durum or soft wheat), 4 oenological Saccharomyces cerevisiae strains (17290 and 14061 isolated from Negroamaro; 9502 and 9518 from Susumaniello musts), and 2 concentrations of sucrose for refermentation (6 and 9 g/L). If maximizing the total phenolic content is the goal, the best beers were those obtained from the mixtures containing durum wheat and fermented by S. cerevisiae 17290 and 14061. Instead, the best sensory results were obtained from brewing the mixture containing the unmalted common wheat and fermented by S. cerevisiae 9518 thanks to their persistent foam; high turbidity, alcohol content, effervescence, and body; and low saltiness and sourness. The physico-chemical and sensory quality of beers were mainly affected by the cereal mixtures and secondarily by yeasts. The quantity of sucrose added for refermentation affected only CO2, residual sugar, and foam.