Policy Points Current efforts to reduce infant mortality and improve infant health in low‐ and middle‐income countries (LMICs) can benefit from awareness of the history of successful early 20th‐century initiatives to reduce infant mortality in high‐income countries, which occurred before widespread use of vaccination and medical technologies. Improvements in sanitation, civil registration, milk purification, and institutional structures to monitor and reduce infant mortality played a crucial role in the decline in infant mortality seen in the United States in the early 1900s. The commitment to sanitation and civil registration has not been fulfilled in many LMICs. Structural investments in sanitation and water purification as well as in civil registration systems should be central, not peripheral, to the goal of infant mortality reduction in LMICs. Context Between 1915 and 1950, the infant mortality rate (IMR) in the United States declined from 100 to fewer than 30 deaths per 1,000 live births, prior to the widespread use of medical technologies and vaccination. In 2015 the IMR in low‐ and middle‐income countries (LMICs) was 53.2 deaths per 1,000 live births, which is comparable to the United States in 1935 when IMR was 55.7 deaths per 1,000 live births. We contrast the role of public health institutions and interventions for IMR reduction in past versus present efforts to reduce infant mortality in LMICs to critically examine the current evidence base for reducing infant mortality and to propose ways in which lessons from history can inform efforts to address the current burden of infant mortality. Methods We searched the peer‐reviewed and gray literature on the causes and explanations behind the decline in infant mortality in the United States between 1850 and 1950 and in LMICs after 2000. We included historical analyses, empirical research, policy documents, and global strategies. For each key source, we assessed the factors considered by their authors to be salient in reducing infant mortality. Findings Public health programs that played a central role in the decline in infant mortality in the United States in the early 1900s emphasized large structural interventions like filtering and chlorinating water supplies, building sanitation systems, developing the birth and death registration area, pasteurizing milk, and also educating mothers on infant care and hygiene. The creation of new institutions and policies for infant health additionally provided technical expertise, mobilized resources, and engaged women's groups and public health professionals. In contrast, contemporary literature and global policy documents on reducing infant mortality in LMICs have primarily focused on interventions at the individual, household, and health facility level, and on the widespread adoption of cheap, ostensibly accessible, and simple technologies, often at the cost of leaving the structural conditions that determine child survival largely untouched. Conclusions Current discourses on infant mortality are not informed by lessons from history. Although structural interventions were central to the decline in infant mortality in the United States, current interventions in LMICs that receive the most global endorsement do not address these structural determinants of infant mortality. Using a historical lens to examine the continued problem of infant mortality in LMICs suggests that structural interventions, especially regarding sanitation and civil registration, should again become core to a public health approach to addressing infant mortality.