Chronic rhinosinusitis (CRS) is a prevalent and disabling paranasal sinus disease associated with some environmental factors. In this study, we evaluated the effect of geo-climatic factors on CRS in a region of southwest Iran. The study mapped the residency addresses of 232 patients with CRS who lived in Kohgiluyeh and Boyer-Ahmad province and had undergone sinus surgery from 2014 to 2019. The effects of Mean Annual Humidity (MAH), Mean Annual Rainfall (MAR), Mean Annual Temperature (MAT), maximum MAT (maxMAT), minimum MAT (minMAT), Mean Annual Evaporation (MAE), wind, elevation, slope, and land cover were assessed on the occurrence of CRS using Geographical Information System (GIS). Statistical analysis was performed using univariate and multivariate binary logistic regression. Patients came from 55 points including villages, towns, and cities. In univariate analysis, climatic factors including MAT (OR = 0.537), minMAT (OR = 0.764), maxMAT (OR = 0.63), MAR (OR = 0.994), and MAH (OR = 0.626) were significantly related to CRS occurrence. Elevation (OR = 0.999), slope (OR = 0.9), and urban setting (OR = 24.667) were the significant determinants among geographical factors when analyzed independently. The multivariate analysis found maxMAT (OR = 0.5), MAR (OR = 0.994), elevation (OR = 0.998), and urban (OR = 16.8) as significant factors affecting CRS occurrence. The urban setting is the most critical factor affecting CRS disease. Cold and dry areas and low attitude are the other risk factors for CRS in Kohgiluyeh and Boyer-Ahmad province, southwest Iran.