[4] The county was established in 1858 and named in honor of Augustin Smith Clayton (1783–1839), who served in the United States House of Representatives from 1832 until 1835.

ValuJet Airlines was headquartered in northern, unincorporated Clayton County, near Hartsfield Jackson Atlanta International Airport, in the 1990s.

A grand jury investigated and considered possible criminal indictments against the Clayton County School Board.

School Board Chairwoman Ericka Davis announced her resignation on April 2, 2008, amidst the allegations.

[27] Amid controversy and orders for the police to quiet citizens, the Clayton County School Board hired a new temporary superintendent on April 26, 2008.

The Clayton County Police Department has an authorized strength of 525 personnel headed by Chief Kevin Roberts.

[34] Other law enforcement services (courts, jail, warrants) are provided by the Clayton County Sheriff's Office.

[35] On April 26, 2021, Sheriff Victor Hill was indicted on charges of federal civil rights violations.

[37] On October 26, 2022, Sheriff Victor Hill was found guilty of violating civil rights of jail detainees.

Tara Boulevard was named for the plantation; it is the main north–south road through the county, carrying U.S. 41 and lesser-known State Route 3.

The fictional Twelve Oaks Plantation and others mentioned in these novels are located in and around Clayton County.

[citation needed] Parts of the film Smokey and the Bandit were shot in and around Clayton County, namely in Jonesboro, as evidenced by a sign in the background of one of the scenes.

Although this particular scene was supposed to be set in Arkansas, a "Willow Bend" sign advertising brick homes in Clayton County can be spotted behind Sheriff George Branford.