Abstract: In recent years, drought-induced tree mortality has occurred in the oak forests of the Zagros Mountains (western Iran). The impacts of climate change induced by drought stress have been most acutely experienced by two populations of Persian oaks (Quercus brantii Lindl) grown in the western provinces (Ilam and Lorestan) of the Zagros region. We surveyed growth, physiological, and biochemical responses of one-year-old Persian oak seedlings from Melasyah (Ilam) and Chegeni (Lorestan) provenances, which were subjected to three watering regimes (100%, 40%, and 20% of field capacity) in a greenhouse. The severe drought stress decreased the diameter and height growth, total biomass, net photosynthesis, gas exchange, xylem water potential, maximum Rubisco activity (Vcmax) as well as the maximum PSII photochemical efficiency of the oak seedlings in both populations, but the rate of decrease was greater in Chegeni seedlings as compared to Melasyah seedlings. Although proline and soluble sugar contents significantly increased in response to drought in both populations under stress, the rate of increase was higher in Melasyah seedlings as compared to Chegeni seedlings. In addition, the activities of peroxidase, superoxide dismutase, catalase, and ascorbic peroxidase as well as that of phenylalanine ammonia lyase were promoted in both populations under drought stress. However, the incremental rate was higher in the Melasyah population than in the Chegeni population. Under severe drought stress, the MDA content, electrolyte leakage, the content of hydrogen peroxide, and superoxide radical significantly increased in both the populations. The rate of increase, however, was higher in the Chegeni population. Under drought stress, the total phenol and flavonoid contents of Melasyah seedlings were higher than those of Chegeni seedlings. The results showed that Chegeni seedlings are more sensitive than Melasyah seedlings when exposed to a water limitation stress. Our findings suggest that the climate conditions of the Persian oak stands should be considered by nursery managers while creating establishment and restoration programs.