Drought tolerance is a main wheat characteristic in the arid and semi-arid regions of the world. This character is affected with several morpho-physiological traits. Selection based on single secondary trait results in low genetic gain for drought tolerance. To find a comprehensive criterion to take advantage of several effective secondary traits simultaneously, three field experiments were conducted on 45 wheat genotypes under irrigated and drought stress conditions. Among 34 morpho-physiological traits, 14 characters including flag leaf angle, flag leaf width, chlorophyll a, number of grains on the main spike, canopy temperature, leaf temperature, biological yield, stover above ground biomass at harvest, proline content, malondialdehyde content, photosynthetically active radiation, net photosynthetic rate, transpiration rate and leaf stomatal conductance could significantly separate high and low yield genotypes under drought stress condition and entered the discriminant function. Discriminant function with 96.67% accuracy screened low and high grain yield genotypes. In addition, this criterion had a significant positive correlation (r = 0.89**) with grain yield under water-deficit condition. This comprehensive criterion which explained 78% of wheat grain yield variation under drought stress conditions could improve selection efficiency in wheat breeding programs. The results showed that selection based on biological yield, leaf temperature, stover above ground biomass at harvest, leaf stomatal conductance, canopy temperature and malondialdehyde as the most promising traits may enhance a genetic gain for grain yield in environments that are vulnerable to water deficit in the future.