Millions of people worldwide have sickened and died from tuberculosis in recent centuries. Yet for most of human existence, the impact of tuberculosis on society is largely unknown. It is, indeed, unknowable without methods suitable for estimating disease prevalence in skeletal samples. Here such a procedure is applied to medieval and early modern Danish skeletons, and it shows how disease prevalence varied with differences in socioeconomic conditions. The approach is based on sensitivity and specificity estimates from modern skeletons. To augment our understanding of tuberculosis in Danish history, 713 adult skeletons were examined, all from Ribe. Tuberculosis increased from 17% to 40% in the medieval to early modern periods in Ribe. Low status (29%) people were more likely to contract the disease than those of high status (10%). The general model, derived from the modern expression of tuberculosis, fits the early modern sample better than it does the medieval skeletons. Differences in the model's fit indicate the skeletal expression changed over time. Notably, rib lesions increased in frequency from the medieval to early modern periods. The approach developed here can provide insights into host-pathogen relationships and disease expression in future work with tuberculosis and other diseases that affect the skeleton.