In August, 1880, a Post Office was established in Wano, 1½ miles northeast of present St. Francis at the trading post. During late 1887, while the railroad was being constructed, the first buildings were moved from Wano to St. Francis. The site, a Horse Ranch owned by the Lincoln Land Company, was surveyed in 1887 by A. L. Emerson, a New England sea captain who had run away from home to follow the sea at age 16. He led the movement to the new town site and named it in honor of his brother, Francis, who had recently been deceased. The Saint was added later, and the Post Office was officially moved in 1888.

In 1885, Gottlieb and Christina Raile made their home near St. Francis and homesteaded a few years later. Today the Raile name is one of the most prevalent family names in the county.