We explored how mortality scales with city population size using vital registration and population data from 742 cities in 10 Latin American countries and the United States. We found that more populated cities had lower mortality (sublinear scaling), driven by a sublinear pattern in U.S. cities, while Latin American cities had similar mortality across city sizes. Sexually transmitted infections and homicides showed higher rates in larger cities (superlinear scaling). Tuberculosis mortality behaved sublinearly in U.S. and Mexican cities and superlinearly in other Latin American cities. Other communicable, maternal, neonatal, and nutritional deaths, and deaths due to noncommunicable diseases were generally sublinear in the United States and linear or superlinear in Latin America. Our findings reveal distinct patterns across the Americas, suggesting no universal relation between city size and mortality, pointing to the importance of understanding the processes that explain heterogeneity in scaling behavior or mortality to further advance urban health policies.