Identifying and evaluating cultivars for drought tolerance is considered an effective approach to achieving sustainable grape production under water-limited conditions. Therefore, a controlled greenhouse experiment was conducted to evaluate the morphological, physiological and biochemical responses of grapevine (Vitis vinifera L.) cultivars and genotypes to drought stress and distinguish highly tolerant from highly sensitive materials. Irrigation deficits were imposed at 5, 10, and 15 day intervals, corresponding approximately to soil water potentials of –0.2 MPa (mild stress), –0.7 MPa, and –1.2 MPa, respectively, based on preliminary calibration using a soil tensiometer in 18 L pots, in 15 grapevine cultivars, including ‘Fiesta’, ‘Superior’, ‘Perlette’, ‘Angoor Siah’, ‘Shast-Aroos’, ‘Volgo Don’, ‘Fakhri’, ‘Thompson Seedless’, ‘Angoor Siah Mahali’, ‘Angoor Sefid Mahali’, ‘Siah Kollm’, ‘Zard Kollm’, ‘Siah Tak’, ‘Asgari’, and ‘Yaghooti’. In this study, morphological traits, relative water content of leaves, electrolyte leakage, membrane stability, growth indices, photosynthetic pigments, antioxidant enzyme activities, total phenol content, and proline concentration were evaluated. The results indicated that the interaction between drought stress and cultivar was significant for most traits. ‘Siah Tak’, ‘Fiesta’, and ‘Angoor Siah’ were identified as the most drought-tolerant cultivars. These cultivars exhibited high antioxidant enzyme activities and greater proline accumulation. In contrast, ‘Perlette’, ‘Angoor Sefid Mahali’, and ‘Asgari’ exhibited greater sensitivity to water deficit compared with the other cultivars. These findings can provide valuable guidance for selecting suitable grape genotypes for establishing commercial vineyards in Ilam province and other water-limited regions of the country.