The Arkansas Valley in Colorado had been occupied by indigenous people since prehistoric times through the 19th century. The Ute people occupied the upper Arkansas River Valley (north of modern Pueblo, Colorado) while the Apache peoples of the Dismal River Culture occupied lands east of Pueblo. By the 1730s, most of the Apache lands in the Arkansas Valley were occupied by Comanche. During the 19th century, some of the Arapaho and Cheyenne people moved into the Arkansas Valley and they allied with the Comanche. Throughout the 19th century, American and European settlers established small trading posts in the river valley. El Pueblo, also known as Fort Pueblo, was established in 1842. El Pueblo was destroyed by a war party of Utes and Jicarilla Apaches in 1854 and was abandoned shortly thereafter. It was revived during the Colorado Gold Rush of 1859. The town of South Pueblo was incorporated in 1873. The towns of South Pueblo, North Pueblo, and Bessemer consolidated into the city of Pueblo in 1889.

Reverend Joseph W. Pickett was the superintendent of the Congregational Home Missions Society for the Rocky Mountain District during the 1870s. Pickett called on Rev. Thomas McClelland in 1878 to come to Colorado to establish a Congregational church in South Pueblo. He arrived in July and immediately began the work of establishing a church. By September the church was gathered and its first minister, George T. Tomkins, was called. And in 1879, the First Congregational Church of South Pueblo was formally incorporated. The name of the church changed to First Congregational Church after the merger of South Pueblo, North Pueblo, and Bessemer in 1889.

The church’s first building was erected in 1881. By 1888, the church planned to buy four plots of land with the intent of erecting a new church building. The building was designed by Fred A. Hale and construction on the new building began in 1889. The first worship server in the new building occurred on January 19, 1890. The First Congregational Church has continued to worship in the same building to this day; the building was added to the National Register of Historic Places in 1985.

The Minnequa Community Church was formed in 1904 and served its community in Pueblo for more than 40 years. Owing to decreased membership and financial solvency, the Minnequa Community Church merged into the First Congregational Church in 1948. Reverend Jeffery D. Hoy, who severed as pastor between 1949 and 1956, played an important role in the establishment of the Christ Congregational Church in Belmont, Pueblo. In 1957, the First Congregational Church voted to join the newly established United Church of Christ. The First Congregational Church continues to serve the Pueblo community today.