Two autochthonous yeast strains called F-8 and F-78 (isolated and selected from the Tikveš wine-producing region) were inoculated in wine musts from Vranec and Cabernet Sauvignon grape varieties. The fermentation process and quality of the produced wines were compared to the wines produced from the same grape varieties, but with a commercial yeast strain (D-80). The fermentation process was undertaken at 23–25 °C for 16 days. The highest alcohol content was detected in Vranec and Cabernet Sauvignon wines fermented with autochthonous F-8 yeast strain. Conversely, Vranec wine fermented by the F-78 yeast strain contained the lowest alcohol content (14.11%). The low sugar amount (2–3 g/L) in both grape varieties is indicated the production of dry wines. The total amount of phenolic compounds was significantly higher in Vranec wines. Unlike the alcohol content, Vranec wine produced by commercial yeast strain D-80 indicated the highest concentration of total phenolic compounds (1450 mg/L) and total anthocyanins (572 mg/L), while the lowest concentrations were observed in wine fermented by autochthonous yeast strain F-78 (1612 mg/L and 470 mg/L, respectively). The maximum color intensity was measured in the Vranec wine fermented by autochthonous yeast strain F-8, while wines from Cabernet Sauvignon grape variety fermented with the same yeast strain F-8 and commercial yeast strain D-80 had comparable values in terms of color intensity.