DROUGHT has become an important challenge in crop cultivation, so detection of drought-tolerant cultivars by screening existing genotypes is a valuable tool in the effort to attain food security worldwide. The drought stress tolerance of two wheat cultivars was determined through treatments with PEG (−0.4MPa) and SA (0.5mM). The resulting data on seed germination and seedling growth indicated that Misr-2 cultivar is more drought-tolerant than Gemaza-12. Under non-stress conditions, Misr-2 had higher pigment values, higher levels of soluble sugars (Glu, Fru, and Suc) and antioxidant enzyme activity (CAT, APX, POX and SOD), but lower proline values than those in Gemaza-12. Gemmaza-12 had higher expression of proline synthesizing gene (P5CS) but lower expression of proline-degrading genes (ProDH and P5CDH) than Misr-2. Under drought conditions, Gemaza-12 needed more osmoregulators and antioxidants than Misr-2 to minimize the negative effects of drought and associated oxidative stresses. Increase percentages of soluble sugars, proline content and antioxidation enzymes were higher in Gemaza-12 than in Misr-2. Under drought stress, stimulation of P5CS and retardation of ProDH and P5CDH were higher in Gemaza-12 than in Misr-2. Although treatment of stressed plants with SA stimulated P5CS gene in both cultivars, retardation of ProDH and P5CDH was more pronounced in Gemaza-12 than in Misr-2. Consequently, we conclude that seed germination and seedling growth could be used to compare drought tolerance of wheat cultivars and seed soaking in SA improves drought tolerance. Our results confirmed that an increase in proline production is one of the symptoms of drought stress in plants.