To assess the response of promising safflower genotypes to late-season drought stress in delayed planting conditions, an experiment was conducted in two years (2016–2017 and 2017–2018) in Iran. The irrigation regime was specified in two levels, including normal irrigation and irrigation cut off in the seed filling stage in main plots, and five safflower genotypes, including Soffe, Goldasht, Golmehr, Padideh, and Parnian were categorized in subplots. Applied drought stress significantly reduced the seed yield and yield components of all genotypes, which accompanied with a substantial decrease in oil content and oil yield of all genotypes. However, the highest seed and oil yield in drought stress conditions obtained in the Parnian genotype by value 2338 and 561 kg/ha, respectively. Moreover, a significant drought-induced increase in palmitic, stearic, and oleic acids, as well as a decrease in linoleic acid content, was observed in all genotypes. Parnian genotype with high unsaturated fatty acids content (90.9%) and the minimum amount of saturated fatty acids (8.7%) might be a promising genotype to starting a formal crop improvement program to achieve more drought-tolerant safflower genotype.