Water stress is a serious abiotic stress that causes extreme loss of rice yield. Keeping these in view, fifteen hybrids along with their eight parents were evaluated at the experimental farm of Rice Research Department, Sakha, Kafr El-Sheikh, Egypt, during the two rice-growing seasons of 2019 and 2020. The analysis of variance revealed significant differences among the genotypes, crosses, lines, and lines x testers interaction for all the studied traits. Sakha 107 was identified as the potential genotype for improving grain yield under water stress based on mean value and GCA effect. While, Sakha 108 was identified as a good general combiner for improving grain yield and its related traits under irrigated condition. The significant yield reduction was observed under water stress in the majority of the rice genotypes studied. The cross combinations Sakha 107/ APO, Sakha 107/ WAB 96-1-1, Sakha 104/ WAB 96-1-1 and Sakha 101/ APO exhibited significantly low drought susceptibility index (DSI) and high yield stability index (YSI) values based on preliminary screening, and good specific combinations for certain physiological and biochemical traits, were established as genotypes tolerant to water stress. RM260, RM279 and RM514 showed the highest degree of polymorphism in the selected rice genotypes for SSR-based genotyping. Among the studied genotypes tested, the parental lines Sakha 107, IRRI 148, WAB 96-1-1 and APO were found to be more diverse based on their genetic distance. It could be considered and used for marker-assisted breeding programs as a possible water stress tolerant donor.