Soybean (Glycine max L.) is an important oilseed crop but is known to be sensitive to environmental challenges. Soil salinity is known to hamper soybean growth and yield significantly. Through this investigation, we tried to uncover the important insights into physiological, biochemical, and molecular responses and adaptive strategies of two Indian soybean cultivars - MAUS-47 (salt-tolerant) and Gujosoy-2 (salt-sensitive) to salinity stress. In a completely randomized block design experiment, plants of both cultivars were subjected to control (no salt treatment) and salt treatment (100 mM NaCl) at the trifoliate stage (10 plants of each cultivar per treatment with three biological replicates). Salinity stress generated reactive oxygen species (ROS), both free and non-free-radical forms, which seemingly triggered cell death as revealed by spectrophotometric histochemical analyses with significant varietal differences. Cultivars showed differential ROS-scavenging (enzymatic/non- antioxidative machinery) capabilities. The functioning of ion-accumulating channels differed between the two cultivars, with the sensitive cultivar exhibiting a higher intake of Na+ ions, leading to the replacement of essential K+, P+, and Mg2+ ions and thus ionic imbalances. This ion imbalance could be attributed to the yield damage, growth, and developmental delays in the sensitive cultivar under salt stress conditions. The expression pattern of 5 key genes representing salt-overly-sensitive (SOS) pathways, transcription factors, and antioxidant enzymes was revealed by qRT-PCR analysis. Differential expressions were observed for the genes corresponding to Na+/H+ antiporter (SOS1), transcription factors (WRKY and MYB), nitrate reductase-1, and superoxide dismutase (Cu-Zn). These findings thus shed light on the intricate mechanisms underlying salt stress responses in soybean and how tolerant and sensitive cultivars show differential strategies, offering valuable insights for developing salt-tolerant varieties and improved agricultural practices.