Plant genotype, age, size, and environmental factors can modify susceptibility and tolerance to disease. Understanding the individual and combined impacts of these factors is needed to define improved disease management strategies. In the case of Wheat streak mosaic virus (WSMV) in winter wheat, yield losses and plant susceptibility have been found to be greatest when the crop is exposed to the virus in the fall in the central and southern Great Plains. However, the seasonal dynamics of disease risk may be different in the northern Great Plains, a region characterized by a relatively cooler fall conditions, because temperature is known to modify plant–virus interactions. In a 2-year field study conducted in south-central Montana, we compared the impact of fall and spring WSMV inoculations on the susceptibility, tolerance, yield, and grain quality of 10 winter wheat varieties. Contrary to previous studies, resistance and yields were lower in the spring than in the fall inoculation. In all, 5 to 7% of fall-inoculated wheat plants were infected with WSMV and yields were often similar to uninoculated controls. Spring inoculation resulted in 45 to 57% infection and yields that were 15 to 32% lower than controls. Although all varieties were similarly susceptible to WSMV, variations in tolerance (i.e., yield losses following exposure to the virus) were observed. These results support observations that disease risk and impacts differ across the Great Plains. Possible mechanisms include variation in climate and in the genetic composition of winter wheat and WSMV across the region.