Diverse growing season weather in western Canada has large effects on wheat quality. Management practices, such as pesticide application, may also affect wheat quality, but are largely unknown. This study measured pesticide application effects on grain quality for six hard red spring wheat cultivars over three growing seasons at four prairie locations. Each siteyear included (i) an untreated control, (ii) fungicide applied at anthesis for Fusarium head blight (FHB) control, (iii) pre-harvest glyphosate applied at physiological maturity, and (iv) a combination of both pesticides. Generally warmer and drier conditions in 2015 and 2017 compared to 2016 resulted in wheat with higher grades, test weight, thousand-kernel weight, and grain protein content but lower Fusarium damaged kernel (FDK) content. Siteyear, reflecting weather variation by location, was the major factor affecting grain quality, contributing from 39% to 77% of total variance. Rainfall variation was greater than that for air temperature and appeared to be the main weather factor affecting quality. Genotype had a significant impact on grain quality but contributed 1%–20% of total variance. The pesticide treatments had a significant effect on several quality parameters, but they contributed only 0.2%–2% to total variance, implying that they have no detrimental effect on wheat grain quality when applied as recommended. Fungicide significantly reduced FDK level in four of ten siteyears, all with high FDK levels, but not when applied at the low FDK siteyears. Fungicide for FHB control should be used only when weather is conducive to high FHB disease pressure.