The effect of fungicides on severity of sudden death syndrome (SDS; caused by Fusarium virguliforme), plant establishment, and soybean yield was evaluated in 12 field experiments conducted in Illinois, Indiana, Iowa, Michigan, and Ontario in 2013 and 2014. Two soybean cultivars that differed in susceptibility to SDS were planted in fields with a history of SDS or with artificial augmentation of F. virguliforme. Efficacy of seed, in-furrow, and foliar-applied fungicides was assessed. SDS levels varied across locations and years. Fluopyram applied on the seed or in-furrow reduced foliar disease index maximum up to 95% in 5 of the 12 experiments. In three experiments with significant (P < 0.10) treatment effect, fluopyram seed treatment improved yields up to 11% compared with the base seed treatment comprising prothioconazole + penflufen + metalaxyl and clothianidin + Bacillus firmus. Meta-analysis also indicated that the fluopyram seed treatment and in-furrow application were effective at reducing SDS and increasing yield relative to the control; however, the baseline disease influenced the yield and disease response to fungicide treatments. Treatment effect was not significant when disease pressure was low. The concentration of F. virguliforme DNA in soybean roots, measured by a specific real-time quantitative polymerase chain reaction assay, was not different among fungicide treatments in 9 of 10 experiments. Moderately resistant cultivars had less disease than susceptible cultivars, indicating that resistant cultivars in combination with fluopyram seed treatment or in-furrow application could provide effective management of SDS.