Water stress may affect the growth, physiology, morphology, biochemistry, and productivity of Nigella sativa (black cumin), a medicinal and aromatic plant. Measuring these parameters under various irrigation regimes could provide useful information for successful genotype selection and breeding. Therefore, these agronomically significant features were evaluated in ten black cumin genotypes (Afghanistan, Pakistan, Syria, India, Arak, Isfahan, Semirom, Shahreza, Shahrekord, and Mashhad) under three irrigation regimes (40% (I1), 60% (I2), and 80% (I3) of permissible moisture discharge) during the 2017 to 2018 growing seasons. Water stress was shown to increase the levels of carotenoids (Cars), proline, total soluble carbohydrates (TSC), malondialdehyde (MDA), hydrogen peroxide (H2O2), catalase (CAT), and ascorbate peroxidase (APX) activities but reduced the relative water content (RWC) and chlorophyll content. The highest increases in Cars, TSC, proline, CAT, and APX were noted in the Arak, Isfahan, Semirom, Shahreza, Shahrekord, and Mashhad genotypes under the I3 water regime, respectively. At the same time, the lowest decrease was observed in chlorophyll, H2O2, and relative water content (RWC) in Semirom. According to the stress susceptibility index, the most resistant genotypes were Shahrekord under I2 and Semirom under I3. These data demonstrate that the irrigation regimes affected the physiological, biochemical, and morphological features of black cumin both qualitatively and quantitatively, although the impact varied depending upon the genotype, irrigation regime, and traits. As such, the results presented represent valuable information with which to inform future selection and breeding programs for drought-tolerant black cumin. This is of particular significance considering global climate change.