The name Isleta is Spanish for "little island". The Spanish Mission of San Agustín de la Isleta was built in the pueblo in 1612 by Spanish Catholic Franciscans. It is one of the oldest mission churches in the United States. When the Spanish returned to New Mexico after the Pueblo Indian Revolt of 1680, they found the church destroyed, except for the nave.

The church was rebuilt in 1716 on the foundation of the old church. During the Pueblo Revolt of 1680, many of the pueblo people had fled to Hopi settlements in Arizona, while others followed the Spanish retreat south to El Paso del Norte (present-day El Paso), Texas. After the rebellion, the Isleta people returned to the Pueblo, many with Hopi spouses. Later in the 1800s, friction with members of Laguna Pueblo and Acoma Pueblo, who had joined the Isleta community, led to the establishment of the satellite settlement of Oraibi. Today, as well as the main pueblo, Isleta includes the small communities of Oraibi and Chicale.

The pueblo’s modern enterprises include the Isleta Resort & Casino, a large casino complex with 100,000 square feet of gambling space, five restaurants, big-name and local entertainment (box office: 505-244-8191), a sports bar, and a gift shop, (800) 460-5686, (505) 724-3800.

The tribe runs the Isleta Eagle Golf Course, a championship 27-hole golf course with beautiful panoramic views, (505) 848-1900. Fishermen and children delight in the Isleta Lakes Recreational Complex, which is open year-round. Many picnicking and RV campsites are also available; call (505) 244-8102.