Arbutus-berry brandy is a traditional Portuguese distillate that plays a significant role in the regional economy. At present, the fermentation of arbutus-berry must occurs spontaneously, resulting in inconsistency in the quality of the final product. The objective of this study was to characterize Saccharomyces cerevisiae strains isolated from naturally fermented arbutus-berry must, with a view to selecting strains with the potential for controlled and consistent fermentations. A total of 65 strains were evaluated using high-throughput methods, based on 24 phenotypic tests, allowing the selection of 10 strains with distinct profiles. These were then subjected to a series of fermentation tests in synthetic must. Additionally, the same 10 strains were inoculated into arbutus-berry must to conduct fermentation. Subsequent monitoring of the inoculated samples was undertaken over a period of 30 days, during which the weight loss was evaluated. The majority of the strains were distinguished by their accelerated sugar consumption and effective fermentation performance in arbutus must, indicating their potential for industrial application in controlled fermentations for the production of arbutus-berry brandy.