Summary: A pot experiment was conducted in a climate-controlled greenhouse with different salt stress treatments (60, 80, 100, and 120 mM NaCl). The results indicated that exposure to NaCl-induced salinity reduces growth of sorghum cultivars by damaging chlorophyll pigment and chloroplast, particularly at a higher stress level. SSG 59-3 alleviated adverse effects of salinity by suppressing oxidative stress (H2O2) and stimulating enzymatic and non-enzymatic antioxidant activities (SOD, APX, CAT, POD, GR, GST, DHAR, MDHAR, GSH, ASC, proline, GB), as well as protecting cell membrane integrity (MDA, electrolyte leakage). Salinity also influenced Na+ ion efflux and maintained a lower cytosolic Na+/K+ ratio via concomitant upregulation of SbSOS1, SbSOS2, and SbNHX ion transporter genes in sorghum genotypes. Overall, these results suggest that Na+ ions are retained and detoxified and less stress impact was observed in mature and younger leaves. Based on the above, we deciphered that SSG 59-3 performed better by retaining higher plant water status, photosynthetic rate and antioxidant potential and upregulation of ion transporter genes, thereby alleviating stress, which may be augmented as genetic resources to establish sorghum cultivars with improved quality in saline soils.