Despite its promising potential, the capabilities of Saccharomyces paradoxus in commercial winemaking are still unutilized and require further investigation. In this study, the effects of fermentation by a S. paradoxus strain P01-161 on the composition of Malvazija istarska white wine in two harvest years were investigated. A range of complementary standard and metabolomics analysis approaches were applied, including OIV methods for basic parameters; HPLC-DAD-RI for organic acids, glycerol, and proteins; UPLC/MS/MS for phenolic compounds; and GC/FID, GC/MS, and GC × GC/TOF-MS for volatile compounds. The harvest year exhibited a significant impact, but many distinctive traits of S. paradoxus versus S. cerevisiae control wines were consistent across the seasons. These included reductions in malic acid and certain phenols and pathogenesis-related proteins. Saccharomyces paradoxus fermentation yielded higher levels of glycerol, volatile acidity, and specific thaumatin-like proteins. Among a total of 474 identified volatile compounds, S. paradoxus exhibited lower concentrations of several odoriferous alcohols, acids, and esters, as well as higher concentrations of β-damascenone, acetaldehyde, isobutyric acid, ethyl 2-methylbutyrate, ethyl acetate, isobutyl acetate, various esters of succinic and lactic acids, accompanied by numerous minor compounds, when compared to S. cerevisiae. These differences suggest the potential for distinct sensory profiles produced by the two yeasts, indicating that S. paradoxus could be a promising alternative for white wine production.