As of the 2010 census, the city had a population of 2,646.
Originally named Varney after the city's first grain buyer, its name was changed in 1864 to Clio. The name change was brought on by Colonel Hill, a literary minded local hotel owner. Colonel Hill convinced the local ladies to name the town after the Greek goddess Clio, muse of history and poetry and daughter of Jupiter.
On July 23, 2007 Governor Jennifer Granholm announced Clio as a community chosen by the Michigan State Housing Development Authority (MSHDA), to take part in the Blueprints for Downtowns program. Clio will receive a comprehensive, market-driven strategy toward developing an action-oriented downtown that will result in economic growth, job creation and private investments. The Blueprints for Downtowns award, were announced to be also received by the communities of Caro and Ypsilanti. Scottville received a similar award to take part in the Cool Cities Michigan Main Street program.