[5] Keytesville is the hometown of U.S. Army General Maxwell D. Taylor, who commanded the "Screaming Eagles" 101st Airborne division during the Normandy invasion of World War II.

Confederate General Sterling Price, who attacked Keytesville during an unsuccessful cavalry raid across his home state, had previously operated a hotel there.

Keyte also created the town's first industry when he constructed a mill near his home on Mussel Fork Creek.

As a two-story, four-room brick building, it survived until September 20, 1864, when it was burned down by Confederate raiders during the American Civil War.

[7] On September 20, 1864, Confederate General Sterling Price arrived on the outskirts of Keytesville with a force of 250 men, among them George Todd and other members of Quantrill's Raiders[9] under the command of Major John Thrailkill.

This action was part of Price's 1864 campaign that extended across the state from eastern Missouri to the Kansas City area.

When Thrailkill's force arrived, Keytesville was defended by a small Union detachment of 35 men from the Missouri militia, commanded by Lieutenant Anthony Pleyer.

Early on the morning of September 20, under a flag of truce, Thrailkill demanded the surrender of the Union troops, promising fair treatment.

[11] Confederate forces then briefly occupied the town, commandeering supplies from various merchants, burning down the courthouse, and executing Chariton County sheriff Robert Carmon and William Young, a Union scout and alleged spy.

[12] In February 1866, a contract was awarded for construction of a replacement courthouse, a two-story brick building with cupola.

Hugo Bartz and J. J. Moore, secured land and financing for the project, which when completed consisted of two miles of track and a large barn for horses and rolling stock, constructed for a cost of $10,000.

[7] Two horse-drawn passenger coaches and a large flatcar for freight delivered new arrivals at the Wabash depot to the town.

The town has a business district, a public library, and chamber of commerce,[14] swimming pool, insurance sales, bank, convenience store, law offices, chiropractor, restaurant, auto repair, agricultural services and medical clinic.

There are three sites in Keytesville listed on the National Register of Historic Places: the First Presbyterian Church, the Chariton County Jail and Sheriff's Residence, and the Redding-Hill House.

Its enrollment places the Tigers in Class 1 under Missouri State High School Activities Association guidelines.