Tallapoosa is of Creek origin and may mean "grandmother town" in the Muscogee language.

The Tallapoosa branch of the Muscogee tribe is considered one of the oldest groups in the Southeast.

The river was a major population center for the Creek Indians before the early 19th century.

In 1832, Tallapoosa County was created from lands ceded by the Creek Indians in the Treaty of Cusseta.

The forced removal of the Creeks in 1836 and 1837 was followed by a frantic gold rush, bringing a flood of profit seekers and settlers.

The Battle of Horseshoe Bend was fought in the territory that would become Tallapoosa County in 1814.

[5] As of the 2020 United States census, there were 41,311 people, 16,205 households, and 11,183 families residing in the county.

As of the census of 2010, there were 41,616 people, 16,985 households, and 11,762 families living in the county.

Nearly 27.2% of households were made up of individuals, and 11.4% were one person aged 65 or older.

As of the census of 2000. there were 41,475 people, 16,656 households, and 11,809 families living in the county.