Volatile flavor has prompted a great amount of influence in acceptance and view points in fruit products. Melon (Pyrus communis) is an aroma-dense fruit, thus, the evaluation of volatile flavor is crucial to melon-breeding. The volatile compounds present in nine varieties of Xinjiang muskmelons were identified and analyzed using the headspace solid-phase microextraction and gas chromatography-mass spectrometry methods. In addition, transcriptomics were used to discover the differential genes in fatty acid degradation pathways. It was found that a total of 170 volatile substances, including 52 alcohols, 41 esters, 24 aldehydes, 32 ketones, 14 acids and seven phenols, were identified in the nine melons. Results of PCA showed that 3-nonanol, 2-nonanol, bis (2-ethylhexyl) adipate, and 2-methylpropanal contributed more to the flavor of melon. It was verified that high activities of acyl-coenzyme A cholesterol acyltransferase (AAT) promoted the conversion of alcohols to esters, so that the melons have a high content of esters. Four genes of long-chain acyl-CoA synthetase were mainly responsible for the large difference in volatile substances. This practice may further undermine the primary rationale for the breeding and promotion in different cultivars of muskmelon.