Field trials were conducted under natural infection and artificial inoculation from 2012 to 2014 at seven sites across the Canadian prairies to determine genetic and management effects on Fusarium head blight (FHB) in wheat production systems. A system of management, which consisted of (1) a control of no fungicide was compared with (2) the seed treatment (ST) thiamethoxam + difenoconazole + metalaxyl-M + S-isomer, (3) an in-crop foliar fungicide (tebuconazole + prothioconazole), or (4) ST + foliar fungicide, was integrated with four wheat cultivars of contrasting growth habits and levels of FHB resistance. Results indicated the cultivars expressing improved FHB resistance, Carberry (spring wheat) and Emerson (winter wheat), were superior over susceptible cultivars, Harvest (spring wheat) and CDC Falcon (winter wheat), in reducing Fusarium-damaged kernel (FDK) and deoxynivalenol (DON) levels, and displayed higher yield under high Fusarium pressure. Winter wheat displayed higher overall yield, with Emerson producing the highest and most stable yields across environments. Application of foliar fungicide, with or without the ST, increased grain yield, seed mass, and test weight; and lowered FDK and DON. Seed treatment alone increased test weight, spring plant density of both winter wheat varieties, and kernel weight in Emerson. A management strategy of foliar fungicide and (or) ST + foliar fungicide generally produced higher yields with greater stability, particularly for susceptible cultivars in high FHB environments. The results of this study reinforce that integration of FHB-resistant cultivars with appropriate cultural practices is required to reduce the risk of FHB and optimize grain yield, and is further enhanced with a winter vs. spring growth habit.