Worldwide, urbanization constitutes a major and growing driver of global change and a distinctive feature of the Anthropocene. Thus, urban development paths present opportunities for technological and societal transformations towards energy efficiency and decarbonization, with benefits for both greenhouse gas (GHG) and air pollution mitigation. This requires a better understanding of the intertwined dynamics of urban energy and land use, emissions, demographics, governance, and societal and biophysical processes. In this study, we address several characteristics of urbanization in Santiago (33.5°S, 70.5°W, 500 m a.s.l.), the capital city of Chile. Specifically, we focus on the multiple links between mobility and air quality, describe the evolution of these two aspects over the past 30 years, and review the role scientific knowledge has played in policy-making. We show evidence of how technological measures (e.g., fuel quality, three-way catalytic converters, diesel particle filters) have been successful in decreasing coarse mode aerosol (PM10) concentrations in Santiago despite increasing urbanization (e.g., population, motorization, urban sprawl). However, we also show that such measures will likely be insufficient if behavioral changes do not achieve an increase in the use of public transportation. Our investigation seeks to inform urban development in the Anthropocene, and our results may be useful for other developing countries, particularly in Latin America and the Caribbean where more than 80% of the population is urban.