The United States has maintained diplomatic relations with Mexico since 1823, when Andrew Jackson was appointed Envoy Extraordinary and Minister Plenipotentiary to that country.

Jackson declined the appointment, however, and Joel R. Poinsett became the first U.S. envoy to Mexico in 1825.

Normal diplomatic relations between the United States and Mexico have been interrupted on four occasions: In addition, the U.S. legation in Mexico was headed by an interim Chargé d'Affaires from April 1864 to August 1867, during the final years of the French Intervention.

The following is a list of Ambassadors the United States has sent to Mexico, and other representatives that have served a similar function.

William Shaler participated in the 1812–13 Gutiérrez–Magee Expedition, which was a private military campaign to overthrow the Royalists and resulted in the roadside murder of two provincial governors and about a dozen other officials.