Temperatures that deviate from the long-term local norm affect human health, and are projected to become more frequent as the global climate changes¹. There are limited data on how such anomalies affect deaths from injuries. In the present study, we used data on mortality and temperature over 38 years (1980–2017) in the contiguous USA and formulated a Bayesian spatio-temporal model to quantify how anomalous temperatures, defined as deviations of monthly temperature from the local average monthly temperature over the entire analysis period, affect deaths from unintentional (transport, falls and drownings) and intentional (assault and suicide) injuries, by age group and sex. We found that a 1.5 °C anomalously warm year, as envisioned under the Paris Climate Agreement², would be associated with an estimated 1,601 (95% credible interval 1,430–1,776) additional injury deaths. Of these additional deaths, 84% would occur in males, mostly in adolescence to middle age. These would comprise increases in deaths from drownings, transport, assault and suicide, offset partly by a decline in deaths from falls in older ages. The findings demonstrate the need for targeted interventions against injuries during periods of anomalously warm temperatures, especially as these episodes are likely to increase with global climate change.