Cadmium (Cd) is a toxic heavy metal that is absorbed from the soil through roots and transmitted through the food chain, posing a serious threat to human health and food security. Exogenous NaCl can reduce the uptake of Cd by plants, but the underlying molecular mechanism is still unclear. In this study, we elucidated the molecular mechanism by which exogenous NaCl inhibited Cd absorption in wheat seedlings. Notably, 50 mM NaCl altered the wheat physiological response and reduce the Cd uptake by plants. Overexpression of the NaCl–responsive gene TaNHX2 increased the levels of chlorophyll and proline, enhanced antioxidant enzyme (CAT, POD, and SOD) activity, decreased the MDA content, and improved tolerance to Cd stress in transgenic wheat plants. We further found that TaWRKY13 binds directly to the TaNHX2 promoter to regulate its transcription. Subsequent research found that TaWRKY13 can also bind to the promoter of the heavy metal transporter gene TaHMA2 to activate its expression. TaNHX2 overexpression obviously downregulated the expression of TaHMA2 in the presence of both NaCl and Cd. In vivo and in vitro assays revealed that NaCl inhibited the binding of TaWRKY13 to the TaHMA2 promoter. This work reveals that NaCl and Cd antagonize uptake at the molecular level and provides new insights for future reductions in Cd accumulation in wheat.