Saline irrigation is one of the approaches that was developed to address the freshwater gap in many regions around the world. This experiment was conducted in two growing seasons under open field conditions in pots. In addition to the control (0.5 dSm-1), three levels of saline water, i.e., 5.0, 7.0, and 9 dSm-1 were used to irrigate ten commercially grown Egyptian wheat cultivars. The number of days to flowering, plant height, fertile tillers, grain weight per spike, number of kernels per spike, and grain yield were measured. Furthermore, Na+, K+, Ca+2, Mg+2, and Cl− were also measured. The objectives of the current study were to (a) estimate the quantitative impact of various levels of saline irrigation water on physio-agronomical performance of commercially grown wheat cultivars; (b) highlight the importance of using salinity stress tolerant wheat cultivars in a scenario where they grow beside salinity stress-sensitive ones and are irrigated with multiple levels of saline water. Salinity stress tolerant wheat cultivars tend to maintain higher levels of K+, Ca+2, and Mg+2, compared to the sensitive ones. Overall, the average performance of the salinity stress-tolerant cultivars across the levels of saline water used was 26.5% higher than the sensitive ones for grain yield. Our results also indicated that 6.25 dSm-1 is the maximum saline water that can be used to irrigate the sensitive wheat cultivars. In which 6.25 dSm-1 is the salinity level that maximizes grain yield, the number of fertile tillers, and K+ concentration while minimizing Na+ accumulation in plants. For the same reasons, nine dSm-1 was defined as the salinity threshold for the salinity stress-tolerant cultivars.