The intensification of summer drought expected with climate change can induce metabolism modifications in plants to face such constraints. In this experiment, we used both a targeted approach focused on flavonoids, as well as an untargeted approach, to study a broader fraction of the leaf metabolome of Quercus pubescens exposed to amplified drought. A forest site equipped with a rainfall exclusion device allowed reduction of natural rainfall by ~30% over the tree canopy. Leaves of natural drought (ND) and amplified drought (AD) plots were collected over three seasonal cycles (spring, summer, and autumn) in 2013 (the second year of rain exclusion), 2014, and 2015. As expected, Q. pubescens metabolome followed a seasonal course. In the summer of 2015, the leaf metabolome presented a shifted and early autumnal pattern because of harsher conditions during this year. Despite low metabolic modification at the global scale, our results demonstrated that 75% of Quercus metabolites were upregulated in springs when trees were exposed to AD, whereas 60 to 73% of metabolites (93% in summer 2015), such as kaempferols and quercetins, were downregulated in summers/autumns. Juglanin, a kaempferol pentoside, as well as rhododendrin derivatives, were upregulated throughout the year, suggesting an antioxidant ability of these metabolites. Those changes in terms of phenology and leaf chemistry could, in the end, affect the ecosystem functioning.