Safflower (<em>Carthamus tinctorius</em> L.) is an oilseed crop adapted to arid and semiarid regions. In this study, an experiment was performed to evaluate the effects of water deficiency on plant height, 1,000-grain weight, seed yield, harvest index, relative water content (RWC), oil yield, and oil content in 15 safflower genotypes. A split-plot randomized complete blocks design was arranged with three replications. Safflower plants were grown under normal irrigation and water deficit conditions in Sarvestan, Fars Province, Iran during 2016 and 2017 growing seasons. Combined analysis results indicated that water deficit stress had negative effects on all measured indices. Average seed yield declined by 65.91% (2,337.91 to 796.79 kg ha⁻¹) due to water deficit stress. Genotype also had a significant effect on evaluated indices, and the interaction between genotype and irrigation significantly influenced all indices except plant height. Under both conditions, highest RWC, seed yield, and oil yield were observed in Dincer and PI-537598 genotypes. Maximum plant height and 1,000-seed weight in both irrigation conditions were observed in the Dincer genotype. In the normal irrigation condition, maximum harvest index and oil content were observed in the CW-74 genotype. Thus, Dincer and PI-537598 were classified as the best genotypes (based on seed yield, RWC, and oil yield) under both normal irrigation and water deficit stress conditions.