Declining water resources and climate change pose a severe threat to sustainable food security by reducing the wheat production. It is necessary to disclose and exploit the genetic potential of wheat germplasm for water deficit tolerance with sustainable yield potential. It is essential to breed wheat varieties which adapted to water-deficit conditions and giving the highest yield to fulfil the wheat demand. Therefore, water deficit-tolerant and water deficit-susceptible genotypes were used in line (10) × tester (5) mating design to determine the genetic basis for water deficit tolerance using on physiological and yield-related attributes in different environments. Significant genetic variability was observed in the studied traits under both environments, including flag leaf area, stomata size, stomatal frequency, leaf venation, epidermal cell size, number of grains per spike, 1000-grain weight, and grain yield per plant. The results of specific combining ability analyses were significant, which exhibited the dominance types of gene action in the inheritance of physiological and yield-related attributes. Hence, hybrid breeding will be fulfilling, and sorting for superior genotypes should be as late as in the F4 and F5 generations. Gene action and combining ability-based screening showed that the genotypes G‑9493, G‑9508, and their cross (G-9493 × G-9508) were ideal genetic resources and had the genetic potential to breed drought-tolerant genotypes. These superior genotypes and their cross combination can be combined to produce high-yielding and drought-tolerant wheat genotypes to fulfill the need for wheat and sustainable food security for the growing population.