Protection from fungal plant pathogens is key for optimizing the yield and quality of wheat (Triticum aestivum L.). However, current grower practices and historical research do not always align with respect to optimum fungicide timing to maximize disease control, yield, quality, and profitability of Canadian Western Red Spring (CWRS) wheat. Six fungicide treatments were evaluated at eight site–years across Alberta in 2018 and 2019 to determine the optimum time for fungicide application. The treatments included early fungicide applications at BBCH 22–23 (herbicide timing), early- to mid-season application at BBCH 30–32 (plant growth regulator timing), ‘traditional’ timing at BBCH 39–45 (flag leaf), and head timing at BBCH 61–63 (Fusarium head blight timing) and were compared with a non-treated control. Yield responses to fungicide treatments occurred at 50% of the site–years when disease pressure was 32% higher than in non-responsive site–years. Responsive site–years were characterized by higher relative humidity (65.4%–74.0%) and an average 273 mm of precipitation. At responsive site–years, McFadden leaf spot disease severity ratings were 50% greater in early August when fungicides were applied at BBCH 22–23 and 30–32 versus at BBCH 39–45. At responsive sites, yield and thousand-kernel weight were 9.3% and 5.2%, higher, respectively, for fungicide applications at BBCH 39–45 and BBCH 61–63 compared with fungicide applications at BBCH 22–23 and BBCH 30–32. The most economically beneficial practices were applications of propiconazole, benzovindiflupyr and azoxystrobin (Trivapro A+B) at BBCH 39–45 or prothioconazole and tebuconazole (Prosaro XTR) at BBCH 61–63 when environmental conditions were conducive for disease development.