Abstract: In order to explore the metabolic and lipidomic changes of tobacco leaves during aging, an integrated analytical approach using both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) was used to chemically profile flue-cured tobacco leaves from different origins. The results showed that primary metabolites such as carbohydrates, amino acids, lipids, and nucleotides decreased significantly in tobacco leaves after aging, however, increased abundance of secondary metabolites including flavonoids, benzenoids, phenols, and terpenoids was observed. Additionally, during the aging time of 1 to 7 years, the above mentioned primary metabolites continuously decreased with the extension of aging time, while the secondary metabolites showed an opposite trend. The cultivar YY87, which was cultivated in Guangdong and Hunan, showed great chemical compositional differences atdifferent cultivation origins. These differences were attributed to amino acids and membrane lipids, however, the differences decreased after aging. In conclusion, the metabolomics and lipidomics methods can effectively distinguish aged and nonaged tobacco leaves, reveal the characteristics of tobacco leaves with different aging degrees, and the effects of different producing areas on the chemical composition of tobacco leaves.