Clio's beginning was almost by accident. Until the building and completion of the Flint and Pere-Marquette Railway in 1861, Clio's history was comparatively uneventful. Pine forests occupied a portion of its site, and hundreds of acres of the same valuable timber were standing in its immediate vicinity, but the stupid cupidity which actuated one or two men in or near the old village of Pine Run during the building of the railways was Clio's opportunity, and this new avenue of commerce, which would have more fully developed and built up a neat little village, already an important trading and manufacturing point, was divided from its proposed route. Pine Run was given the go-by and the station of Clio was established in its place.

In 1862 the Flint and Pere Marquette Railroad built its original 26.1-mile section of track from Saginaw to Mount Morris. It selected Clio, originally known as Varna, as a railroad station location. The area around Varna was covered with white pine. The railroad thrived on the shipment of logs, lumber, and wood products.