Fusarium head blight (FHB) and its associated deoxynivalenol (DON) contamination of grains are recurrent wheat production problems in subtropical, humid southern Brazil. Cooperativa Agraria Agroindustrial from Guarapuava, PR, Brazil, developed an integrated management system for FHB and DON by combining pre-harvest and post-harvest strategies. The pre-harvest strategies include genetic resistance, different sowing dates, chemical control, a regional climate and disease monitoring network, and improved spray technology. The post-harvest strategies include rules and standards for grain reception, including rapid mycotoxin determination in truckloads, proper grain cleaning, drying and storage, grain peeling, and further processing in the wheat mill. Among the pre-harvest strategies, genetics stands out through screening resistance of wheat genotypes against FHB and DON contamination in wheat grains and whole grain flour (WGF). The genetic resistance approach considers resistance type I – resistance against initial infection; type II – resistance to pathogen spreading in spike; type III – resistance to kernel infection; type IV – tolerance against FHB; and type V – resistance to toxins. The main question was how to reduce mycotoxin levels in wheat grains and WGF based on more tolerant wheat genotypes. Eight commercial cultivars and pre-commercial genotypes were evaluated in a randomized complete block design with three replications from 2017 to 2021. The plot area was 5.1 m², and overhead sprinkler irrigation supplemented the natural moisture needed for infection and disease development. Plants were artificially inoculated at mid-anthesis by spraying a spore suspension with a concentration of 5x10⁴ conidia/mL. The inoculum was a pool of isolates representing trichothecenes genotypes of the Fusarium graminearum species complex occurring in the southern Paraná state. The analysis of variance of the FHB index and DON revealed significant effects of growing season, cultivar, as well as for the interaction among these factors (P ≤ 0.02). Significant differences (P<0.05) among wheat genotypes were observed in the FHB index and WGF DON. WGF DON reduction provided by genetic resistance over seasons with less severe to more severe epidemics ranged from 377 ppb to 82 ppb (78.2% reduction) and from 5618 ppb to 2750 ppb (51.5% reduction), respectively. This study showed that genetic resistance was more effective in seasons with less severe FHB epidemics and is a valuable control measure for the integrated management of FHB and DON in southern Brazil.