The Osage and Missouri were in the territory at the time of earliest European contact, which was mostly by French explorers and traders.

Displacing the Osage, the Shawnee had a major village known as Chillicothe about a mile from the present-day city, named after their historic capital in their traditional lands in Ohio.

[6] Chillicothe was incorporated as a city by an act of the General Assembly, approved March 1, 1855.

In August of that year an order was made to erect the first Court House, the cost not to exceed $5,000, in the Public Square; The first circuit court for the trial of civil and criminal causes was held on the 3d of July 1887.

[7] Livingston was settled by emigrants from the older counties and others from the Upper South states of Kentucky and Tennessee, as well as Ohio and other "Old Northwest" states, as the westward migration continued.

Prior to completion of the Hannibal & St. Joseph Railroad in 1859, the city was minimally developed with cheap frame houses, with little pretense of architectural beauty or design.

Soon two and three-story brick business buildings were constructed in place of the former frame structures.

From that time on Chillicothe made a slow, steady growth up to 1886, when the Chicago, Milwaukee & St. Paul Railroad was built through here.

That year also saw the introduction of the "Water Works" and electric lights.

The last passenger train passed through Chillicothe in 1971, when the American Royal Zephyr between Chicago and Kansas City was discontinued.

The 1909 Depot was owned by the City of Chillicothe until 2016, when it was sold to Wabash BBQ to be used as a restaurant.

The Grand River flows past approximately one mile south of the city and the confluence of the Thompson River with the Grand is about three miles to the southwest.

[12] The 2020 United States census[16] counted 9,107 people, 3,608 households, and 2,044 families in Chillicothe.

There were 4,114 housing units at an average density of 577.0 per square mile (222.6/km2).

Of all households, 35.5% consisted of individuals and 18.6% had someone living alone who was 65 years of age or older.

35.5% of all households were made up of individuals, and 17.2% had someone living alone who was 65 years of age or older.

35.9% of all households were made up of individuals, and 18.9% had someone living alone who was 65 years of age or older.