The emergence of chronic wasting disease, an infectious prion disease of multiple deer species, has motivated international calls for sustainable, socially accepted control measures. Here, we describe long-term, spatially replicated relationships in Colorado, US, mule deer (Odocoileus hemionus) herds that show hunting pressure can modulate apparent epidemic dynamics as reflected by prevalence trends. Across 12 areas in Colorado studied between 2002–18, those with the largest declines in annual hunting license numbers (pressure) showed the largest increases in the proportion of infected adult (≥2–yr-old) male deer killed by hunters (prevalence); prevalence trends were comparatively flat in most areas where license numbers had been maintained or increased. The mean number of licenses issued in the 2 yr prior best explained observed patterns: increasing licenses lowered subsequent risk of harvesting an infected deer, and decreasing licenses increased that risk. Our findings suggest that harvesting mule deer with sufficient hunting pressure might control chronic wasting disease—especially when prevalence is low—but that harvest prescriptions promoting an abundance of mature male deer contribute to the exponential growth of epidemics.