This paper documents changes in infant mortality (IM) rates in São Paulo, Brazil, between 2003 and 2013 and examines the association among neighborhood characteristics and IM. We investigate the extent to which increased use of health care services and improvements in economic and social conditions are associated with reductions in IM. Using data from the Brazilian Census and the São Paulo Secretaria Municipal da Saúde/SMS, we conducted a longitudinal analysis of panel data in all 96 districts of São Paulo for every year between 2003 and 2013. Our regression model includes district level measures that reflect economic, health care and social determinants of IM. We find that investments in health care have contributed to lower IM rates in the city, but the direct effect of increased spending is most evident for people living in São Paulo’s middle- and high-income neighborhoods. Improvements in social conditions were more strongly associated with IM declines than increases in the use of health care among São Paulo’s low-income neighborhoods. To reduce health inequalities, policies should target benefits to lower-income neighborhoods. Subsequent research should document the consequences of recent changes in Brazil’s economic capacity and commitment to public health spending for population health.