Alkalinity stress is a very common occurrence in both semiarid and arid climates. It not only slows crop growth but also reduces yields significantly. A hydroponic screening technique was used to identify the genetic variation in growth, physio-biochemical, and ionic homeostasis caused by alkalinity stress in wheat cultivars under 0 mM, 40 mM, and 80 mM alkaline stress conditions using NaHCO3:Na2CO3 with a ratio of 9:1. The results showed that alkalinity stress significantly decreased the root length of wheat cultivars by 20.05% and 46.07%, shoot length by 25.91% and 50.16%, root fresh weight by 30.84% and 41.79%, shoot fresh weight by 18.91% and 41.80%, root dry weight by 43.63% and 60%, and shoot dry weight by 20.28% and 46.95%, at 40 mM and 80 mM, respectively, in comparison with the control. Likewise, alkalinity stress significantly increased K+ ion accumulation and decreased water relations and photosynthetic attributes. It also enhanced the rate of lipid peroxidation, Na+ ion concentration, action of antioxidant enzymes, proline concentration, and sugars under stress conditions. The Akbar-2019 variety performed comparatively better than the rest of the cultivars under stress situations in terms of growth, biomass, antioxidant potential, and biochemical cationic characteristics. Hence, it is concluded that Akbar-2019 is the most recommended alkaline-tolerant suitable cultivar due to its better tolerance in varied soil environments affected by alkalization.