The first recorded settlement of Acuña took place on 27 December 1877. It was actually founded by a group of colonists led by Domingo Urias, Irineo Casillas Arevalo, and his wife Maximina Espinoza. At the same time, the Governor of the State was general Hipólito Charles who posted a military garrison in the area led by Captain Manuel Leal. In 1880 the community received villa (town) status under its first name of Garza Galán. In 1884 the locality was renamed Congregación las Vacas. Congregacion Las Vacas was then renamed Villa Acuña in 1912 after Saltillan poet Manuel Acuña. Villa Acuña was finally given the title of city on 16 September 1951 By Don Jesus, when it got its present name of Ciudad Acuña.
On 24 October 1960, US president Dwight D. Eisenhower and Mexican President Adolfo López Mateos met in Acuña to sign the initial agreements allowing construction of the dam. Construction plans were not finalized until December 1966 when presidents Lyndon B. Johnson and Gustavo Díaz Ordaz met on the international bridge. Presidents Richard M. Nixon and Gustavo Díaz Ordaz met for the dedication of Amistad Dam on 8 September 1969.
Originally created to serve airmen at Laughlin AFB just across the border, "Boy's Town" is an entertainment district that is located in an area south of Ciudad Acuna and contains a few after-hours bars and brothels, but is designated off-limits to U.S. military personnel
