Invasive Cronobacter infections among infants are associated with severe neurologic disabilities and death. Early Cronobacter reports typically featured hospitalized and preterm infants and recognized contaminated powdered infant formula (PIF) as a transmission vehicle. To clarify recent epidemiology, we reviewed all cases of bloodstream infection or meningitis among infants that were reported to the Centers for Disease Control and Prevention and in the literature (1961–2018; n = 183). Most infants were neonates (100/150 [67%]); 38% (42/112) died, and 79% (81/102) had reported recent PIF consumption. In the final quarter of the study period (2004–2018), case counts were significantly higher (global average 8.7 cases/year); among US cases, significantly higher proportions occurred among full-term (56% [27/48]) and nonhospitalized (78% [42/54]) infants. PIF contamination, most commonly from opened containers, was identified in 30% (21/71) of investigations. Our findings reaffirm the need to promote safer alternatives for infant feeding, particularly among neonates.