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This study revealed a climate-driven shift in pathogen dominance from Alternaria spp. to Fusarium spp., determining associated toxin chemotypes. Untargeted LC\u2013MS metabolomics of wheat infected by Fusarium graminearum (wild-type vs \u0394Tri5) identified host-derived metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) and rutin, as key toxin-suppressing candidates. Both compounds strongly inhibited mycotoxin biosynthesis (&amp;gt;95%) with minimal antifungal activity. Mechanistic analyses showed that rutin disrupted toxisome structure, impairing metabolic flux required for deoxynivalenol (DON) production despite active Tri gene expression. Field trials further demonstrated that disease symptom reduction alone does not ensure toxin control. However, combining difenoconazole with rutin effectively decoupled fungal growth from toxigenesis, reducing NIV accumulation by 89.92%. 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