Climate change threatens biodiversity as populations can persist if they migrate or adapt to the rapidly changing conditions of the Anthropocene. However, the metabolic mechanisms underlying plant population persistence under the long-term trends of increasing temperature and drought remain unclear. Here, we investigate the persistence and adaptation of yarrow (Achillea millefolium L.) populations over 100 years of climate change. We resurveyed historical sites spanning a broad climatic gradient (from 1 m to 3200 m above sea level) and analyzed metabolic diversity in a common-garden experiment. We report that nine out of ten populations persisted locally, showing phenotypic and metabolic differentiation. The only population potentially extirpated is that of the hottest and driest site. A complex interaction between increasing temperatures and changing precipitation patterns shaped plant growth across populations. Populations from warmer sites in coastal and mountain regions grew taller than 100 years ago, whereas populations from drier sites in lowlands and foothills became shorter. Furthermore, we document differentiation in metabolic diversity involving plant defenses and stress response. These findings suggest that ongoing adaptation is constrained by long-term changes in temperature and precipitation as well as by local biotic interactions. Preserving locally adapted populations and their metabolic diversity is key for conservation efforts in the face of accelerating climate change.