Hydrogen sulphide (H2S), a crucial gas signal molecule, has been reported to be involved in various processes related to development and adversity responses in plants. However, the effects and regulatory mechanism of H2S in controlling Fusarium head blight (FHB) in wheat have not been clarified. In this study, we first reported that H2S released by low concentrations of sodium hydrosulphide (NaHS) could significantly alleviate the FHB symptoms caused by Fusarium graminearum (F. graminearum) in wheat. We also used coleoptile inoculation to investigate the related physiological and molecular mechanism. The results revealed that FHB resistance was strongly enhanced by the H2S released by NaHS, and 0.3 mM was confirmed as the optimal concentration. H2S treatment dramatically reduced the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) while enhancing the activities of antioxidant enzymes. Meanwhile, the relative expressions levels of defence-related genes, including PR1.1, PR2, PR3, and PR4, were all dramatically upregulated. Our results also showed that H2S was toxic to F. graminearum by inhibiting mycelial growth and spore germination. Taken together, the findings demonstrated the potential value of H2S in mitigating the adverse effects induced by F. graminearum and advanced the current knowledge regarding the molecular mechanisms in wheat.