Saccharomyces cerevisiae and S. uvarum are two domesticated species of the Saccharomyces sensu stricto clade that diverged around 100 Ma after whole-genome duplication. Both have retained many duplicated genes associated with glucose fermentation and are characterized by the ability to achieve grape must fermentation. Nevertheless, these two species differ for many other traits, indicating that they underwent different evolutionary histories. To determine how the evolutionary histories of S. cerevisiae and S. uvarum are mirrored on the proteome, we analyzed the genetic variability of the proteomes of domesticated strains of these two species by quantitative mass spectrometry. Overall, 445 proteins were quantified. Massive variations of protein abundances were found, that clearly differentiated the two species. Abundance variations in specific metabolic pathways could be related to phenotypic traits known to discriminate the two species. In addition, proteins encoded by duplicated genes were shown to be differently recruited in each species. Comparing the strain differentiation based on the proteome variability to those based on the phenotypic and genetic variations further revealed that the strains of S. uvarum and some strains of S. cerevisiae displayed similar fermentative performances despite strong proteomic and genomic differences. Altogether, these results indicate that the ability of S. cerevisae and S. uvarum to complete grape must fermentation arose through different evolutionary roads, involving different metabolic pathways and duplicated genes.