Fusarium head blight (FHB) of cereals is one of the most important pre-harvest diseases worldwide. One possible method to reduce the intensity of FHB and mycotoxin levels is to apply fungicides to wheat at the flowering stage. This paper reports the efficacy of fungicides to control FHB and reduce the associated mycotoxin biosynthesis. In a two-year experiment eight combinations of fungicides were tested. Ear inoculation with a suspension of conidia of Fusarium culmorum representing the DON chemotype, confirmed by PCR assay, was conducted during anthesis. All fungicides significantly reduced FHB severity. The best control and the highest wheat yield were obtained after the application of spiroxamine + prothioconazole at GS 29-32, combined with prothioconazole + fluoxastrobin at GS 49-55 (yield 166.5% of the control) or tebuconazole and prothioconazole (165.8%). All the other protection programs resulted in higher yields (117.1–138.5% of the control). A clear relation was observed between the disease intensity and mycotoxin concentrations.