Yield loss and toxin contamination caused by wheat Fusarium head blight (FHB) have always been a worldwide concern. Cultivating disease-resistant varieties and fungicide application are effective measures to control FHB. The comprehensive control technology system for FHB and toxin contamination of wheat in Anhui Province needs further improvement. This study compared the control efficacy of different wheat varieties, fungicides and application times on wheat FHB and deoxynivalenol (DON) contamination, and the dynamic change of DON accumulation after application. Among the 93 main wheat varieties in Anhui Province, the disease-resistant and low-toxic wheat variety "Ningmai 26" was more suitable for planting in the central part of Anhui Province. At the same time, "Yangmai 22" was used for subsequent experiments. The field efficacy trials of different fungicides showed that 30% prothioconazole oil dispersion (OD) had the highest control efficacy on FHB and DON contamination, reaching 94.33 and 77.49%, respectively. The study on the optimum application time of prothioconazole showed that the 0-20% flowering stage was the key point of DON control. The survey of the dynamic changes of DON accumulation showed that prothioconazole could significantly reduce the level of DON accumulation while inhibiting the accumulation rate of DON. At the same time, the control fungicide carbendazim increased the level of DON contamination. This study will provide excellent germplasm resources for cultivating disease-resistant and low-toxic wheat varieties, and provide a theoretical reference for establishing a collaborative prevention and control system of disease control and toxin reduction. © 2023 Society of Chemical Industry.