The male disadvantage in infant mortality underwent a surprising rise and fall in the 20th century. Our analysis of 15 developed countries shows that, as infant mortality declined over two centuries, the excess male mortality increased from 10% in 1751 to >30% by approximately 1970. Remarkably, since 1970, the male disadvantage in most countries fell back to lower levels. The worsening male disadvantage from 1751 until 1970 may be due to differential changes in cause-specific infant mortality by sex. Declines in infant mortality from infections and the shift of deaths to perinatal conditions favored females. The reduction in male excess infant mortality after 1970 can be attributed to improved obstetric practices and neonatal care. The additional male infants who survived because of better conditions were more likely to be premature or have low birth weight, which could have implications for their health in later life. This analysis provides evidence of marked changes in the sex ratio of mortality at an age when behavioral differences should be minimal.