Understanding the geographic distribution of mosquito‐borne disease and mapping disease risk are important for prevention and control efforts. Mosquito‐borne viruses (arboviruses), such as West Nile virus (WNV), are highly dependent on environmental conditions. Therefore, the use of environmental data can help in making spatial predictions of disease distribution. We used geocoded human case data for 20042017 and population‐weighted control points in combination with multiple geospatial environmental data sets to assess the environmental drivers of WNV cases and to map relative infection risk in South Dakota, USA. We compared the effectiveness of (1) land cover and physiography data, (2) climate data, and (3) spectral data for mapping the risk of WNV in South Dakota. A final model combining all data sets was used to predict spatial patterns of disease transmission and characterize the associations between environmental factors and WNV risk. We used a boosted regression tree model to identify the most important variables driving WNV risk and generated risk maps by applying this model across the entire state. We found that combining multiple sources of environmental data resulted in the most accurate predictions. Elevation, late‐season humidity, and early‐season surface moisture were the most important predictors of disease distribution. Indices that quantified interannual variability of climatic conditions and land surface moisture were better predictors than interannual means. We suggest that combining measures of interannual environmental variability with static land cover and physiography variables can help to improve spatial predictions of arbovirus transmission risk.