Abstract: To achieve target metabolome changes in flue-cured tobacco strips during aging, tobacco strips from different domestic production areas were sampled and studied using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry at 8 sampling time points across 31 months (August 2018 to April 2021) to track their natural aging process in the aging warehouse of China Tobacco Guangdong Industrial Limited Corporation. The results showed that the metabolome of different tobacco strips showed a consistent pattern of chemical changes with aging. The weighted gene co-expression network analysis (WGCNA) divided all the metabolites into 27 modules with the characteristics of the aging duration, and more modules were significantly correlated with the early or late stages of aging. From the 5 modules found to be significantly correlated with at least 4 of the aging durations, 59 hub metabolites were identified, including lipids, aroma components, dipeptides, terpenes, and flavonoids. More specifically, the lipid contents gradually decreased, the contents of some terpenes and small molecule acids, ketones and other aroma components gradually increased, the microorganisms on the surface of tobacco leaves became more active, and the contents of dipeptides gradually increased with the progress of aging. This study provides important data for a comprehensive understanding of the chemical changes in tobacco leaves during natural warehouse aging, and the hub metabolites identified are of great application for monitoring the aging process, controlling the quality of aged tobacco, and optimizing the aging duration.