Chronic wasting disease (CWD) is a prion disease of cervids that spreads to uninfected individuals through direct transmission (contact with infected individuals), vertical transmission (from mother to offspring), or indirect transmission (exposure to contaminated environments). The risk of indirect transmission is unevenly distributed on the landscape, and risk levels are expected to be controlled by patterns of habitat use by infected and uninfected individuals as well as environmental properties that alter the length of time prions remain infectious and available for uptake. Despite evidence from controlled or laboratory studies identifying environmental properties likely to affect patterns of CWD prion locations on the landscape, it remains difficult to connect mechanisms to realized increased or decreased risk of disease transmission, and few studies have attempted to detect patterns of different CWD risk in different environments. Using data from GPS-collared mule deer in Wyoming that were CWD-tested annually, we constructed models predicting annual probability of disease transmission contingent on environmental properties extracted from GPS use points. We compared models that emphasized different pathways of disease transmission by including or excluding sets of covariates that described deer density, habitat selection, and covariates expected to affect prion persistence in the environment. Results indicated that key habitat characteristics often selected by mule deer, such as proximity to secondary roads, were also associated with higher risk of testing positive for CWD, which supports the hypothesis that disease risk was correlated to patterns of habitat use by deer. We also found increased risk associated with spatial properties that were not selected-for by deer, such as areas where topography collects moisture, suggesting that prion retention mechanisms also play a role in risk. Incorporating these spatially-varying risk factors into our understanding of CWD transmission and outbreak progression can support managers in designing data collection and disease management strategies.