Distillation fractions (head, body, and tail) and mezcal samples were analyzed by proton nuclear magnetic resonance spectroscopy (1H-NMR). Samples were obtained from five rural producers in Oaxaca State, Mexico, where the distilled beverage was produced using as raw material Agave angustifolia, commonly known as “Espadín”. The distillation cuts were done by the producers according to their experience and samples were taken from each distillation fraction. 1H-NMR spectra were acquired by two sample preparation methods: direct analysis (DA) and solid-phase extraction (SPE) using styrene–divinylbenzene sorbent to concentrate aromatic compounds. When DA-NMR was used, fifteen compounds were identified and quantitated at mg/L level, including higher alcohols, aldehydes, esters, and organic acids. On the other hand, nine compounds were identified by SPE-NMR, including fatty acids, aromatic alcohols, aldehydes, and polycyclic aromatic hydrocarbons. The study showed that 1H-NMR can be done by DA and with SPE as a complementary method for analysis of mezcal and its distillation fractions. These methodologies are useful for both research and industrial purposes.