PREMISE OF THE STUDY:Autopolyploidy, or whole‐genome duplication, is a recurrent phenomenon in plant evolution. Its existence can be inferred from the presence of massive levels of genetic redundancy revealed by comparative plant phylogenomics. Whole‐genome duplication is theoretically associated with evolutionary novelties such as the development of new metabolic reactions and therefore contributes to the evolution of new plant metabolic profiles. However, very little is yet known about the impact of autopolyploidy on the metabolism of recently formed autopolyploids. This study provides a better understanding of the relevance of this evolutionary process.METHODS:In this study, we compared the metabolic profiles of wild diploids, wild autotetraploids, and artificial autotetraploids of Arabidopsis thaliana using targeted ultra‐high performance liquid chromatography‐triple quadrupole‐ mass spectrometry (UPLC‐QqQ‐MS) metabolomics.KEY RESULTS:We found that wild and artificial A. thaliana autotetraploids display different metabolic profiles. Furthermore, wild autotetraploids display unique metabolic profiles associated with their geographic origin.CONCLUSIONS:Autopolyploidy might help plants adapt to challenging environmental conditions by allowing the evolution of novel metabolic profiles not present in the parental diploids. We elaborate on the causes and consequences leading to these distinct profiles.