Corpus Christi de la Isleta, the first mission and pueblo in Texas, was established by Antonio de Otermín and Fray Francisco de Ayeta in 1682 and was maintained by Franciscans for Christianizing the Tigua Indians, who accompanied Otermín on his retreat to the El Paso area after his unsuccessful attempt to recover New Mexico in the winter of 1681–82. To the Tiguas, the mission church is known as San Antonio, after their patron saint, and they call the pueblo Ysleta del Sur. The site was also known by the Spaniards as Corpus Christi de la Isleta. The present church was constructed in 1851. Its distinctive silver-domed bell tower was added in 1897. In 1881 the Jesuits took over the church and renamed it Nuestra Señora del Monte Carmelo. Fire severely damaged the structure in 1907, but it was soon repaired.
The mission pueblo is estimated to have been 3½ leagues southeast of the site of modern Ciudad Juárez. Shortly after its founding as an Indian pueblo, twenty-one families of Spaniards were living at Ysleta. At that time Ysleta was on the south side of the Rio Grande. There, on May 19, 1692, Gov. Diego de Vargas granted possession of the church and convento to the Catholic Church in the person of Fray Joaquín de Hinojosa. For the next 160 years Franciscan missionaries were constant in their ministry to the spiritual needs of the people of Ysleta, but frequent shifting of the main channel of the river resulted in changes in location of the settlement. In 1726 and again in 1766 the inspectors Pedro de Rivera y Villalón and the Marqués de Rubí respectively, reported Ysleta on the east and then north side of the river. In 1758, however, Ysleta was located by Bernardo de Miera y Pacheco on the south bank of the Rio Grande. The most significant move, however, occurred in the period from 1829 to 1831. As a result of flooding, the river altered its course to the south and west, leaving Ysleta on the north bank of the main channel. Because the old channel was also active, Ysleta, Socorro, and San Elizario were situated on a twenty-mile-long island that ranged in width from two to four miles. According to the 1841 census Ysleta had 731 inhabitants: 456 Spanish and 275 Indians. By the terms of the 1848 Treaty of Guadalupe Hidalgo, the main current of the Rio Grande was the international boundary between the United States and Mexico; hence Ysleta became United States territory.
In 1878, in the aftermath of the Salt War of San Elizario, Ysleta replaced San Elizario as county seat of El Paso County; in 1884 El Paso became county seat. In the interest of preserving tribal culture, the Tiguas drew up a constitution and set of bylaws to it in 1895. The most dramatic change in life in Ysleta in modern times, however, followed the completion of Elephant Butte dam in 1916 and the subsequent development of an extensive irrigation system. A rising water table, increased soil salinization, and the onset of San Jose scale in fruit trees led to the substitution of a salt-tolerant variety of cotton for the traditional vineyards and orchards of the area by the late 1920s. Gradually, the community lost its agricultural land as the urban environment grew. In 1955 Ysleta, with a population of some 40,000, was annexed by El Paso over the protests of the residents. The Texas legislature recognized the Tiguas as an Indian tribe and requested transfer of federal responsibility for them to the state in 1967. The following year President Lyndon B. Johnson recognized the tribe and transferred responsibility to the State of Texas.