Pomelo is a common fruit grown in the Mekong Delta, Vietnam which is famous for its delicious taste and a variety of healthy nutrients. Among pomelo-derived products, wine fermentation can add commercial value to this specialty and improve farmers' income. This study aimed to select a suitable commercial yeast Saccharomyces cerevisiae for the application in wine fermentation from Nam Roi pomelo (Citrus grandis L.). Optimization of fermentation conditions was designed by the multiple regression and the response surface methods in which factors included yeast concentrations, total dissolved solids, and pH levels. As a result, S. cerevisiae BV818 was selected to have the best fermentation ability among seven commercial yeast strains. Pomelo wine was successfully fermented using S. cerevisiae BV818 yeast with an initial total dissolved solid content of 30°Brix, pH of 5.0, and initial yeast level of 0.06% w/v at room temperature (28-32°C) for nine days. Pomelo wine had an ethanol content of 13.24% v/v and good sensory characteristics with an aroma and bright yellow color. Suitable conditions for wine fermentation proposed by this study can contribute to further studies on upscale pomelo-wine productions.