It is well known that the flavor of skim milk is inferior to whole milk due to the lack of fat. With the popularity of low-fat dairy products, improving the flavor of skim milk is a main focus for food scientists. During the production of skim milk, preheating treatments have a significant effect for the flavor of skim milk. In this study, to explore the optimal processing conditions, milk was preheated at 30 °C, 40 °C, 50 °C, 60 °C for 30 min prior to defatting. When the optimal temperature was determined, milk was then preheated at the optimal temperature for 10 min, 20 min, 30 min, 40 min and 50 min, respectively, to obtain the best preheating time. Distinctions between skim milk samples with different processing conditions were studied by sensory evaluation, e-tongue and HS-SPME-GC-MS analysis. Principle components analysis (PCA) and cluster analysis (CA) were selected to associate with e-tongue results and compare the similarities and differences among the skim milks. Sensory and e-tongue results matched and both showed that a preheating temperature of 50 °C and 30 min time might be the optimal combination of processing conditions. Thirteen volatiles, including ketones, acids, aldehydes, alcohols, alkanes and sulfur compounds, were analyzed to evaluate flavor of the skim milks produced by different preheating treatments. Combined with previous studies, the results indicated that most volatile compounds were decreased by reducing the fat concentration and the typical compound 2-heptanone was not detected in our skim milk samples.