Urban centers in Latin American often face high levels of air pollution as a result of economic and industrial growth. Decisions with regard to industry, transportation, and development will affect air pollution and health both in the short term and in the far future through climate change. We investigated the pollution health consequences of modest changes in fossil fuel use for three case study cities in Latin American: Mexico City, Mexico; Santiago, Chile; and São Paulo, Brazil. Annual levels of ozone and particulate matter were estimated from 2000 to 2020 for two emissions scenarios: (1) business-as-usual based on current emissions patterns and regulatory trends and (2) a control policy aimed at lowering air pollution emissions. The resulting air pollution levels were linked to health endpoints through concentration–response functions derived from epidemiological studies, using local studies where available. Results indicate that the air pollution control policy would have vast health benefits for each of the three cities, averting numerous adverse health outcomes including over 156,000 deaths, 4 million asthma attacks, 300,000 children’s medical visits, and almost 48,000 cases of chronic bronchitis in the three cities over the 20-year period. The economic value of the avoided health impacts is roughly $21 to $165 billion (US). Sensitivity analysis shows that the control policy yields significant health and economic benefits even with relaxed assumptions with regard to population growth, pollutant concentrations for the control policy, concentration–response functions, and economic value of health outcomes. This research demonstrates the health and economic burden from air pollution in Latin American urban centers and the magnitude of health benefits from control policies.