Screening of wheat genotypes for drought stress is common, but there is still limited information for diagnostic physiological and morphological parameters linked with improved yield under drought stress. We evaluated the responses of five bread and synthetic wheat genotypes for drought stress under in vitro and in vivo experimental conditions with the aim of finding out the changes in morphological and physiological characteristics. Plants were subjected to osmotic stress under in vitro experiment with the supplement of three concentrations of PEG 6000. Seedlings were grown in three concentrations of PEG 6000 (0% control, 10% and 20%) for 18 days. Measurements of germination percentage, germination index, seed vigor index, mean germination time, shoot length, root length, and chlorophyll content were recorded. These genotypes were also subjected to drought stress under in vivo conditions by withholding water at the booting stage. Plant height, spike length, number of tillers, number of grains, grain yield parameters, and biomass were recorded. Drought stress caused a noticeable decline in germination, growth, yield, and yield contributing parameters. The drought stress had destructive effects on wheat seedlings. The results also indicated that the measured parameters might be considered as promising indicators in assessing wheat genotypes against drought tolerance.