The role of external nitrogen source (NO3- or NH4+) against salinity-promoted damage on photosynthetic machinery and primary metabolism was investigated in Sorghum bicolor L. Sorghum growth was severely decreased by salinity, but the damage was less pronounced in NH4+-fed plants. Closely, NH4+ nutrition promoted better CO2 uptake rate, associated with higher phosphoenolpyruvate carboxylase activity and maintenance of photosystem II efficiency, as well as better ionic regulation in comparison to NO3- nutrition. In parallel, although NH4+ nutrition induced high basal H2O2 content, minor damage to chloroplast integrity was observed compared to NO3- after saline stress. In non-saline conditions, NH4+-fed plants exhibited more connected network than NO3- nutrition, which led to decreased salt impact in network parameters after salt stress. This may be related to previous changes during acclimatization to NH4+, allowing quick responses to secondary stresses, such as salinity. A metabolite set was significantly modulated by N source under salinity, including amino acids, sugar, and organic acids metabolism that displayed important contribution in response to salt stress. The asparagine amino acid was considered a key metabolite in alleviating NH4+ toxicity. Despite the unchanged antioxidant enzymes system, NH4+ nutrition increased the content of ascorbic acid, which may contribute to redox homeostasis and protect the chloroplasts against oxidative damage under salinity. Therefore, NH4+ nutrition was able to activate mechanisms involved in photosynthetic efficiency and regulation of important metabolites, which attenuated the deleterious effects of salinity on sorghum plants.