Chronic wasting disease (CWD) was discovered in free-ranging white-tailed deer (Odocoileus virginianus) in south-central Wisconsin in 2002. The current control method for CWD in the state is the harvest of deer from affected areas to reduce population density and lower CWD transmission. We used spatial regression methods to identify factors associated with deer harvest across south-central Wisconsin. Harvest of deer by hunters was positively related to deer density (slope = 0.003, 95% CI = 0.0001–0.006), the number of landowners that requested harvest permits (slope = 0.071, 95% CI = 0.037–0.105), and proximity to the area of highest CWD infection (slope = −0.041, 95% CI = −0.056–−0.027). Concomitantly, harvest was not impacted in areas where landowners signed a petition protesting intensive deer reduction (slope = −0.00006, 95% CI = −0.0005–0.0003). Our results suggest that the success of programs designed to reduce deer populations for disease control or to reduce overabundance in Wisconsin are dependent on landowner and hunter participation. We recommend that programs or actions implemented to eradicate or mitigate the spread of CWD should monitor and assess deer population reduction and evaluate factors affecting program success to improve methods to meet management goals.