Settlers arrived in Round Valley in the late 1850s. A new settlement formed, initially known as Round Valley, and then Craball. In 1863, Brigham Young visited the community and made a recommendation that it be moved away from the mountains to provide better protection from Indians. The community was ultimately moved to a new site at the center of the valley in 1863, where a townsite was laid out with a central plaza. It then took the new name of Scipio, after Scipio A. Kenner. In March 1869, an LDS ward was established.

In 1866, an Indian raid prompted construction of Fort Scipio; the one-room homes that were already standing were connected by mud walls to provide protection. These homes lasted until 1886, when they were dismantled to rebuild.

Scipio maintained a stable, small population of between 500 and 600 after the turn of the century, reaching a peak of 595 in 1940. Its location along Highway 91 (later Interstate 15) gave rise to service stations to serve travelers. In 1971, Highway 50 was also routed through Scipio. Today, around 330 people live in the quiet community, and a handful of historic buildings and homes remain.