Fusarium head blight (FHB), caused primarily by Fusarium graminearum (Schwabe), is one of the most significant diseases of hard red spring wheat (HRSW) in North Dakota. Implementing integrated management practices such as host resistance and fungicides can be used to manage FHB and the associated mycotoxin deoxynivalenol (DON). However, depending on the production year in North Dakota, both management tools might not be needed for FHB. The objective of this research was to evaluate fungicide premixes and varietal resistance on suppression of FHB, suppression of DON, and economic response in diverse FHB environments in dryland HRSW. Seven field experiments were conducted at dryland locations from 2019 to 2021. Two HRSW varieties, WB-Mayville (susceptible) and ND-VitPro (moderately resistant) served as the main plots, and seven fungicide treatments, including a nontreated control, served as the subplots. Based on disease levels and local weather data (relative humidity, rainfall, and temperature), field experiments were categorized into four FHB management environments (high, moderate, low, and no disease) to assess the effectiveness of management tools in field situations faced by HRSW growers. The fungicide premixture treatments of metconazole + prothioconazole and pydiflumetofen + propiconazole provided similar or better suppression of FHB and DON when compared with FHB fungicide standards. The results suggest that the use of fungicides on a moderately resistant variety provided a more favorable economic response when compared with their use on a susceptible variety in moderate and low FHB environments. The results from this study will help guide FHB management decisions in dryland HRSW.