The population was 21,901 at the 2010 census. It is the only city in Ross County and the center of the Chillicothe Micropolitan Statistical Area (as defined by the United States Census Bureau in 2003). Chillicothe is a designated Tree City USA by the National Arbor Day Foundation.
The town's name comes from the Shawnee Chala·ka·tha, named after one of the five major divisions of the Shawnee people, as it was the chief settlement of that tribal division. The Shawnee and their ancestors inhabited the territory for thousands of years prior to European contact. At the time of European-American settlement, the community was plotted by General Nathaniel Massie on his land grant.
Modern Chillicothe was the center of the ancient Hopewell tradition, which flourished from 200 BCE until 500 CE. This Amerindian culture had trade routes extending to the Rocky Mountains. They built earthen mounds for ceremonial and burial purposes throughout the Scioto and Ohio River valleys. Later Native Americans who inhabited the area through the time of European contact included Shawnees. Present-day Chillicothe is the most recent of seven locations in Ohio that bore the name, because it was applied to the main town wherever the Chalakatha settled.
It was after the American Revolution that most European settlement came to this area. Migrants from Virginia and Kentucky moved west along the Ohio River in search of land. Chillicothe served as the capital of Ohio from the beginning of statehood in 1803 until 1810 when Zanesville became the capital for two years. The capital was moved to Zanesville as part of a state legislative compromise to get a bill passed. In 1812 the legislature moved the capital back to Chillicothe. In 1816 the state legislature voted to move the capital again, to Columbus to have it near the geographic center of the state, where it would be more accessible to most citizens.
Migrants to Chillicothe included free blacks, who came to a place with fewer restrictions than in the slave states. They created a vibrant community and aided runaway slaves coming north. As tensions increased prior to the breakout of the American Civil War, the free black community at Chillicothe maintained stations and aid to support refugees on the Underground Railroad. Slaves escaping from the South traveled across the Ohio River to freedom, and then up the Scioto River to get more distance from their former homes and slave hunters. White abolitionists aided the Underground Railroad as well.