The Hohokam Indians discovered the fertile banks along the Gila River where ideal for growing crops. The Indian village lived here centuries before Father Francisco Eusebio Kino rode through. Father Kino visited in 1699 and helped establish the first farm.

Then in 1774, Spanish Captain Juan Bautista de Anza and Father Francisco Tomas Garces passed by and discovered the rancheria. The rancheria was using the water from the Gila River to sustain the crops. The two travelers named the place Pueblo de los Santos San Simon y Judas. It soon became a popular place for those passing through. In 1858, Gila Bend became a stop along the overland stage route. During the 18th century, the Gila Trail became the major thoroughfare in Arizona . Many famous individuals passed through town such as Kit Carson, General Stephen W. Kearny and Captain Philip St. George Crooke.

However, agriculture was always the town's mainstay. Cotton, alfalfa and grain are the most common crops grown. The town was incorporated in 1962. Today, both agriculture and traveling tourists make Gila Bend a busy town. Many travelers heading to Rocky Point or San Diego from Phoenix use Gila Bend as the place to take a breather.