Fusarium head blight (FHB) is a devastating fungal disease of wheat worldwide causing yield losses and grain contamination with mycotoxins that jeopardise food and feed safety. Field experiments using mulch layers or botanicals were conducted in two consecutive years to investigate prevention measures with the potential to suppress FHB and reduce mycotoxins in wheat. We simulated a system with high disease pressure, i.e. maize-wheat rotation under no-tillage, by applying maize residues artificially inoculated with Fusarium graminearum in field plots after wheat sowing. For mulch layers, a novel cut-and-carry biofumigation approach was employed. Cover crops grown in separate fields were harvested in autumn, chopped and applied directly onto the inoculated maize residues after wheat sowing. Mulch layers of white mustard (Sinapis alba), Indian mustard (Brassica juncea) or berseem clover (Trifolium alexandrinum) were applied. Botanicals included aqueous extracts of white mustard seed flours or milled Chinese galls and were applied to inoculated maize residues after wheat sowing in autumn or at wheat tillering in spring. Mulch layers of white mustard, Indian mustard or clover consistently suppressed Fusarium infection in both years and decreased mycotoxin contents in wheat grain, i.e. deoxynivalenol by up to 50 %, 58 % and 56 %, and zearalenone by up to 76 %, 71 % and 87 %, respectively. Botanicals were more effective in the second year, when the disease pressure was higher, reducing deoxynivalenol and zearalenone contents in grain by 22%–42% and 60%–78%, respectively. However, there were no clear differences between autumn and spring applications of botanicals on disease pressure and mycotoxin contamination. Mulch layer treatments improved grain yield up to 15 % compared with the positive control, while the botanicals had a minor impact on crop yield. Within the context of sustainable crop protection, cereal growers could benefit from the recommended prevention strategies by decreasing the risk of mycotoxin contamination in harvest products and thus improving grain yield and quality.