The World Health Organization recognizes Puerto Rico as an area of low tuberculosis (TB) incidence, where TB elimination is possible by 2035. To clarify the current low incidence of reported cases, provide key lessons learned, and detect areas that may affect progress, we systematically reviewed the literature about the history of TB surveillance and control in Puerto Rico and supplemented this information with additional references and epidemiologic data. We reviewed 3 periods: 1898–1946 (public health efforts before the advent of TB chemotherapy); 1947–1992 (control and surveillance after the introduction of TB chemotherapy); and 1993–2015 (expanded TB control and surveillance). Although sustained surveillance, continued care, and use of newly developed strategies occurred concomitantly with decreased reported TB incidence and mortality rates, factors that may affect progress remain poorly understood and include potential delayed diagnosis and underreporting, the effects of government debt and Hurricane Maria, and poverty.