Objective. To identify key social determinants of tuberculosis (TB) incidence among countries in Latin America and the Caribbean (LAC), a geographic area regarded as one of the most socioeconomically unequal in the world. Methods. An ecological study was conducted at the country level. Data were obtained from several institutional-based sources. Random-effects regression modeling was used to explore the relationship between several social determinants indicators and TB incidence rates in 20 LAC countries in 1995-2012. Standard gap and gradient metrics of social inequality in TB incidence among countries in 2000, 2005, and 2010 were then calculated. Results. TB incidence rate trends were significantly associated with health expenditure per capita and access to improved sanitation facilities, as well as with life expectancy at birth and TB detection rate, after adjusting for other socioeconomic, demographic, and health services variables. Absolute and relative inequality in TB incidence remained mostly unchanged: countries at the bottom 20% of both health expenditure and sanitation coverage distributions concentrated up to 40% of all TB incident cases, despite a considerable decline in the overall TB incidence mean rate during the period assessed. Conclusions. Along with the intensity of TB control (reflected by TB detection rate), both access to sanitation (as a proxy of quality of living conditions) and health expenditure per capita (either as an indicator of the level of resources and/or commitment to health care) appear to be key determinants of TB incidence trends in LAC countries. Inequalities in both health expenditure per capita and access to sanitation seem to define profound and persistent inverse gradients in TB incidence among LAC countries.