Seed soaking is a viable solution for reducing cadmium (Cd) levels in wheat, given the limited options for economically controlling it. This study aimed to explore the precise mechanisms behind seed priming to reduce Cd levels in wheat seedlings via plant ionomics, transcriptomics, and high-throughput sequencing technologies. The results showed that seed soaking with Mn 2+ (100 μM) significantly improved the growth parameters of wheat seedlings. Seed priming with Ag + (1, 2 μM) significantly decreased Cd levels in the roots (32.9 and 40.6%, respectively) and stems (19.4 and 20.3%, respectively), whereas seed priming with Zn 2+ (10 mM) and Mn 2+ (20, 100 μM) significantly decreased Cd levels in the leaves (29.4, 15.6, and 33.5%, respectively) compared to that in the control group. These varied reductions of Cd in wheat seedlings induced by seed soaking were attributed to the restructuring of gene transcription involved in Cd absorption and the recruitment of the genus Rhizopus (plant-beneficial fungi tolerant to Cd) in the rhizosphere soil. It shows that seed soaking could effectively control Cd absorption by wheat in a weakly alkaline soil.