The volatiles of muskmelon (Cucumis melo L. reticulatis cv. Mission) were sampled by dichloromethane extraction and dynamic headspace methods and analyzed by gas chromatography (GC) and GC–mass spectroscopy (MS). A total of 34 constituents were identified, with esters contributing 8%–92% of the total volatiles. Butyl propionate, ethyl 3-methylpentanoate, hexadecanoic acid, methyl (methylthio)acetate, propyl butyrate, phenylpropyl alcohol, and vanillin, were recovered only by solvent extraction, while hexanal was only detected using dynamic headspace sampling. Methyl butyrate 35.2%, ethyl acetate 17.1%, butyl acetate 11.6%, ethyl propionate 8.3%, and 3-methylbutyl acetate 6.3% were the major constituents by solvent extraction sampling method. Butyl acetate 35.5%, 3-methylbutyl acetate 20.9%, ethyl acetate 7.3%, 2-butyl acetate 5.6%, and hexyl acetate 3.8% were the major constituents recovered by headspace sampling. Fruit tissue was also separated into five layers (exocarp, outer mesocarp, middle mesocarp, inner mesocarp, and seed cavity) and the volatile constituents differed significantly in content and composition by tissue.