In order to study the effects of different levels of salt stress and nitrogen (N) on physiological mechanisms, carbon isotope discrimination (Delta C-13), and yield of two wheat cultivars (cv.), a two-year field experiment was carried out during 2013-2015. The treatments included three levels of salt stress (1.3, 5.2, and 10.5 dS m(-1)), three levels of N (50, 100, and 150 kg N ha(-1)), and two wheat cultivars, Bam and Toos. Under salt stress, N application (100 and 150 kg N ha-1) produced a significant effect on both cultivars with respect to physiological traits, i.e., net photosynthetic rate (P-n), stomatal conductance (g(s)), chlorophyll index (CI), Na+/K+ ratio as well as the grain yield (GY). The salt-tolerant and -sensitive cultivars exhibited the maximum values of physio-biochemical and yield attributes at 100 and 150 kg N ha(-1), respectively. The results of Delta C-13 showed a significant difference (P<0.001) between wheat cultivars under the control and salt stress. According to our result, salt-tolerant cultivar Bam seems to be more efficient in terms of higher GY, P-n, g(s), CI, and lower Na+/K+ ratio as well as higher Delta C-13 as compared with salt-sensitive cultivar Toos, under salt stress. Therefore, a significant positive correlation that observed between Delta C-13 and GY, indicated that Delta C-13 may be an effective index for indirect selection of yield potential in wheat under irrigation regimes with saline water.