Jacob Smith from Quebec was the first settler to arrive in Genesee County in 1829. Many settlers were attracted to the rich river valley and the promise of fertile farming and productive industry. Clio emerged as a lumber town in 1837 when Theodore P. Dean built the first sawmill. Postmaster David Huyck later named the area Clio but there are no records regarding the origin of the name. Clio was incorporated as a city in 1828.

Despite its image as a farm town, Clio is a regular stop for travelers on I-75 and a budding center of culture. The Clio Cast and Crew, a local theater group, puts on plays every fall and spring. The Clio Electric Youth Theater, a spin-off of the Clio Cast and Crews, also performs twice a year. The enthusiastic Cast and Crew even helped build an Art Center and Amphitheater. Area residents are treated to quality productions at the Amphitheater and enjoy the use of the Aft Center, Historical Center and the Clio Area Youth Sports Complex. Recreational opportunities are plentiful. Bike paths, swimming pools, parks and playgrounds can be found throughout the town and golfers will enjoy the challenging 18-hole Vienna Greens Golf Course.