Foxtail millet (Setaria italica L.) is an important cereal for managing future water scarcity and ensuring food security, due to its strong drought and salt stress resistance owing to its developed root system. However, the molecular responses of foxtail millet leaves to salt stress are largely unknown. In this study, seeds of 104 foxtail millet accessions were subjected to 0.17 mol·L−1 NaCl stress during germination, and various germination-related parameters were analyzed to derive 5 salt-sensitive accessions and 13 salt-tolerant accessions. Hong Gu 2000 and Pu Huang Yu were the most salt-tolerant and salt-sensitive accessions, respectively. To determine the mechanism of the salt stress response, transcriptomic differences between the control and salt-treated groups were investigated. We obtained 2019 and 736 differentially expressed genes under salt stress in the salt-sensitive and salt-tolerant accessions, respectively. The transcription factor families bHLH, WRKY, AP2/ERF, and MYB-MYC were found to play critical roles in foxtail millet’s response to salt stress. Additionally, the down-regulation of ribosomal protein-related genes causes stunted growth in the salt-sensitive accessions. The salt-tolerant accession alleviates salt stress by increasing energy production. Our findings provide novel insights into the molecular mechanism of foxtail millet’s response to salt stress.