Salinity limits the productivity of many crops, including soybean. This study investigated the molecular mechanisms of salt tolerance by comparing the transcriptomic responses to salt stress between a recently identified salt-tolerant (PI 561363) and a salt-sensitive genotype (PI 601984). Leaf tissues were collected at 0 h, 6 h, 24 h, and 48 h after exposure to 150 mM NaCl for RNA sequencing. The tolerant genotype exhibited higher chlorophyll content and lower levels of malondialdehyde (MDA) and peroxidase (POX) activity compared to the sensitive genotype under salt stress. The highest number of differentially expressed genes (DEGs) was identified at 48 h, followed by 6 h and 24 h in both genotypes. The tolerant genotype showed 1,807, 786, and 4,561 DEGs at 6 h, 24 h, and 48 h, respectively, while the sensitive genotype had 1,465, 681, and 5,479 DEGs. Gene ontology analysis revealed enrichment in processes such as ion transport, ethylene signaling, suberin biosynthesis, lipid biosynthesis, and metabolism. Key candidate genes such as GmHAK5, GmGSTU19, GmKUP6, GmTDT, GmCHX20a, GmOST1/SnRK2.6, GmERF98, and GmERF1 were identified as crucial for stress signaling, ion homeostasis, and cellular integrity under saline stress conditions. These results offer insights into the molecular processes that drive salt tolerance in soybeans and highlight potential targets for breeding more resilient soybean varieties.