In order to study the effects of different levels of salt stress and nitrogen (N) on physiological mechanisms, carbon isotope discrimination (?¹³C), 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 ?¹³C 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 Δ¹³C as compared with salt-sensitive cultivar Toos, under salt stress.  Therefore, a significant positive correlation that observed between Δ¹³C and GY, indicated that Δ¹³C may be an effective index for indirect selection of yield potential in wheat under irrigation regimes with saline water.