Maize, as a glycophyte, is hypersensitive to salinity, but the salt response mechanism of maize remains unclear. In this study, the physiological, biochemical, and molecular responses of two contrasting inbred lines, the salt-tolerant QXH0121 and salt-sensitive QXN233 lines, were investigated in response to salt stress. Under salt stress, the tolerant QXH0121 line exhibited good performance, while in the sensitive QXN233 line, there were negative effects on the growth of the leaves and roots. The most important finding was that QXH0121 could reshift Na+from shoots into long roots, migrate excess Na+in shoots to alleviate salt damage to shoots, and also improve K+retention in shoots, which were closely associated with the enhanced expression levels ofZmHAK1andZmNHX1in QXH0121 compared to those in QXN233 under salt stress. Additionally, QXH0121 leaves accumulated more proline, soluble protein, and sugar contents and had higher SOD activity levels than those observed in QXN233, which correlated with the upregulation ofZmP5CR,ZmBADH,ZmTPS1, andZmSOD4in QXH0121 leaves. These were the main causes of the higher salt tolerance of QXH0121 in contrast to QXN233. These results broaden our knowledge about the underlying mechanism of salt tolerance in different maize varieties, providing novel insights into breeding maize with a high level of salt resistance.