Mule deer (Odocoileus hemionus) populations throughout the western United States have experienced unprecedented declines. Desert mule deer were once common in most mountain ranges throughout the Trans-Pecos region of Texas, but desert mule deer have shown a decline over the past 20 years. Previous research has suggested that the declines are likely an indirect result of prolonged drought, however, little information exists on the causative factors leading to the decline. Because mule deer populations have declined at the landscape level, I initiated a study to evaluate region-wide declines of desert mule deer in the Trans-Pecos region. The objective was to evaluate habitat changes (e.g., brush encroachment, habitat fragmentation, land-use patterns) relative to trends of desert mule deer populations. Change detection was performed on remotely sensed imagery for the 9-county region of the Trans-Pecos for periods corresponding to changes in mule deer abundance: mid-1980s, mid-1990s, and mid-2000s. The relationship between changes in landscape features and mule deer populations were evaluated at herd unit and region-wide scales. Changes observed over longer temporal intervals (10 years) were not related to mule deer populations. When observed on a 2-year time interval, negative correlations were found between change in the negative direction and population trends. The results of this project may help resource managers as well as landowners better understand relationships between mule deer populations and landscape-level changes in habitat.