After Honduras gained independence from Spain in 1821, it joined the Federation of Central American States which also included Guatemala, Nicaragua, Costa Rica, and El Salvador.

The first U.S. Minister Resident to present his credentials in Honduras was James R. Partridge on April 25, 1862.

[1] On March 23, 1943, an agreement between the United States and several American Republics including Honduras elevated the status of their legations to embassies.

A tire fire was started outside the main entrance of the embassy on May 31, 2019, amid protests against the privatization of healthcare and education in the country.

[4] In 2022, a Honduran judge approved the extradition of former President Juan Orlando Hernández to the United States on drug-trafficking and weapons charges.