We analyzed chronic wasting disease (CWD) prevalence data from mule deer populations in northcentral Colorado, USA, to discern the likely influences of temporal, spatial, and demographic factors on patterns observed in naturally infected populations. In addition to reaffirming spatial heterogeneity among wintering mule deer subpopulations, we report marked differences in CWD prevalence by sex and age groups as well as clear local trends of increasing prevalence over a 7-yr period. Prevalence of CWD differed by age (yearling vs. adult), sex, and geographic area at two different spatial scales (game management unit or population unit winter range) and increased over time at both geographic scales. Disease status (positive or negative) was not independent of age for males (n = 285, df = 6, χ² = 18.4, P = 0.005) or females (n = 387, df = 8, χ² = 17.2, P = 0.028). Among males, prevalence increased and then declined across age classes, peaking in 5- to 6-yr-old individuals; among females, prevalence showed no definite age-related pattern. Demographic, spatial, and temporal factors all appear to contribute to the marked heterogeneity in CWD prevalence in endemic portions of northcentral Colorado, USA. These factors likely combine in various ways to influence epidemic dynamics on both local and broad geographic scales.