Although sinus problems have long been recognized as the most common respiratory symptoms associated with agricultural work, there is a scarcity of recent studies and/or reliable estimates as to the true prevalence or risk factors of sinus problems related to farming. The aim of this study was to determine the prevalence of sinus problems in farming and non-farming rural populations and further investigate the association of individual (for example life-style, occupational), contextual (e.g., environmental), and important covariates (e.g., age, sex) with sinus problems. A large-scale cross-sectional study was conducted in farm and non-farm residents of rural Saskatchewan, Canada. A logistic regression model based on a generalized estimating equations approach were fitted to investigate the risk factors of sinus problems. Sinus problems were reported by 2755 (34.0%) of the 8101 subjects. Farm residents were more likely to spend their first year of life on farm compared with non-farm residents, and indicated a significantly lower risk of sinus problems. Meanwhile, occupational exposure to solvent and mold were associated with an increased risk of sinus problems. Some health conditions such as allergy and stomach acidity/reflux, family history, and female sex were also related to a higher risk of sinus problems. Farm residents had a significantly lower risk of sinus problems than non-farm residents, likely due to the exposure to farm specific environments in their early life.