This article investigates tuberculosis mortality in Hermoupolis, the capital of the Greek island of Syros, during the period of continuous cause-of-death reporting from 1916 to 1940. Contemporary reports identified Greece as having one of the highest levels of tuberculosis mortality in Europe, with Hermoupolis ranking at the top within the country. In the early twentieth century, Greece launched an anti-tuberculosis campaign, primarily supported by philanthropists due to limited state intervention. The study examines the actions, if any, taken by the local authorities in Hermoupolis and analyzes mortality attributed to tuberculosis by age group and sex. The results reveal that tuberculosis mortality declined across all age groups in the 1930s, particularly among females. Deaths were concentrated in infancy, early adulthood (20–39 years), and the elderly. Clear differences in tuberculosis fatality rates among occupational classes were found, although they did not markedly differ from all-cause mortality patterns. Factors such as the lack of sanitary reforms, poor living standards, inadequate nutrition, and overcrowding could have potentially played key roles in the high tuberculosis mortality in the city. Considering the inefficacy of sanatorium treatment before the mid-1940s, it is plausible that improvements in factory working conditions and the decrease in industrial activity in the city may have contributed to the reduction in tuberculosis mortality in Hermoupolis during the 1930s.