Rennet whey and skim milk were compared as media for fermentation by commercial cheese, yogurt, and probiotic starter cultures. Effect of culture, medium, and their interaction on flavor was assessed and compared by sensory descriptive analysis and headspace volatile analysis by proton transfer reaction-mass spectrometry. In general, the aroma of fermented whey was similar to that of whey separated from fermented milk, indicating a favorable possibility of substituting milk with whey in the manufacture of fermented milk-like beverages. Starter culture significantly affected most sensory characteristics of the products. Key volatile compounds for the characteristic flavor of yogurt, such as acetaldehyde and diacetyl, were not significantly affected by medium when fermented with the yogurt culture, and reached similar levels in both systems. Volatile analysis results were consistent with the results of the sensory evaluation, indicating the high reliability of proton transfer reaction-mass spectrometry in detecting important volatile compounds for aroma. Integration of this sensory and chemical information allows a better understanding of how flavor and related compounds are affected by ingredients or processing, which may be useful for the development of value-added whey products.