Risk of death during the first year of life due to external causes, such as unintentional injury and homicide, may be higher among twins and higher-order multiples than among singletons in the United States. We used national birth cohort linked birth-infant death data (2000-2010) to evaluate the risk of infant mortality due to external causes in multiples versus singletons in the United States. Risk of death from external causes during the study period was 3.6 per 10,000 live births in singletons and 5.1 per 10,000 live births in multiples. Using log-binomial regression, the corresponding unadjusted risk ratio was 1.40 (95% confidence interval (CI): 1.30, 1.50). After adjustment for maternal age, marital status, race/ethnicity, and education, the risk ratio was 1.68 (95% CI: 1.56, 1.81). Infant deaths due to external causes were most likely to occur between 2 and 7 months of age. Applying inverse probability weighting and assuming a hypothetical intervention where no infants were low birth weight, the adjusted controlled direct effect of plurality on infant mortality due to external causes was 1.64 (95% CI: 1.39, 1.97). Twins and higher-order multiples were at greater risk of infant mortality due to external causes, particularly between 2 and 7 months of age, and this risk appeared to be mediated largely by factors other than low-birth-weight status.