In recent decades, heavy metal pollution has become a significant environmental stress factor. Plants are characterized by high biochemical plasticity and can adjust their metabolism to ensure survival under a changing environment. Here we report, to our knowledge, the first gas chromatography-mass spectrometry (GC-MS)-based metabolomics study of Zn-induced stress responses in Amaranthus caudatus plants. The study was performed with root and leaf aqueous methanolic extracts after their lyophilization and sequential derivatization with methoxylamine hydrochloride and N-methyl- N-(trimethylsilyl)trifluoroacetamide. In total, 419 derivatives were detected in the samples, and 144 of them could be putatively annotated. The metabolic shifts in seven-week-old A. caudatus plants in response to a seven-day treatment with 300 µmol/L ZnSO 4·7H 2O in nutrient solution were organ-specific and more pronounced in roots. Most of the responsive metabolites were up-regulated and dominated by sugars and sugar acids. The revealed effects could be attributed to the involvement of these metabolites in osmotic regulation, antioxidant protection and Zn 2+ complexation. A 59-fold up-regulation of gluconic acid in roots distinctly indicated enhanced glucose oxidation due to oxidative stress upon the Zn treatment. Gluconic acid might be further employed in Zn 2+ complexation. Pronounced Zn-induced up-regulation of salicylic acid in roots and shoots suggested a key role of this hormone in stress signaling and activation of Zn stress tolerance mechanisms. Overall, our study provides the first insight into the general trends of Zn-induced biochemical rearrangements and main adaptive metabolic shifts in A. caudatus.