Monitoring the response of wild mammal populations to threatening processes is fundamental to effective conservation management. This is especially true for infectious diseases, which may have dynamic and therefore unpredictable interactions with their host. We investigate the long-term impact of a transmissible cancer, devil facial tumour disease (DFTD), on the endemic Tasmanian devil. We analyse trends in devil spotlight counts and density across the area impacted by the disease. We investigate the demographic parameters which might be driving these trends, and use spatial capture-recapture models to examine whether DFTD has affected home range size. We found that devils have declined by an average of 77% in areas affected by DFTD, and that there is a congruent trend of ongoing small decline in spotlight counts and density estimates. Despite this, devils have persisted to date within each of nine monitoring sites. One site is showing as yet unexplained small increases in density 8–10 years after the emergence of DFTD. We also found the prevalence of DFTD has not abated despite large declines in density and that diseased sites continue to be dominated by young devils. The long-term impact of the disease has been partially offset by increased fecundity in the form of precocial breeding in 1-year-old females, and more pouch young per female in diseased sites. The lower densities resulting from DFTD did not affect home range size. Synthesis and applications. Transmission of devil facial tumour disease continues despite large declines in devil density over multiple generations. Plasticity in life history traits has ameliorated the impact of devil facial tumour disease, however broad-scale trends in density show ongoing decline. In light of this, devil facial tumour disease and the impact of stochastic events on the reduced densities wrought by the disease, continue to threaten devils. In the absence of methods to manage disease in wild populations, we advocate managing the low population densities resulting from disease rather than disease per se.