It was named for the plantation home of Walter Leake, third governor of Mississippi, which was located in Clinton and built in 1812.

Currently Clinton has three major highways that pass through the city: the Natchez Trace Parkway, U.S. Route 80, and Interstate 20.

Mount Hermon Female Seminary, a historically black college, was established in 1875 by Sarah Ann Dickey.

During the Civil War, Confederate forces, as well as Union troops— the latter commanded by generals Ulysses S. Grant and Sherman—briefly occupied Clinton on their way to the Battle of Vicksburg in May 1863.

[9] In September 1875 during the election campaign, a Republican political rally was held in downtown Clinton, where 3,000 people were gathered expecting Governor Adelbert Ames and other prominent speakers.

But election-related violence continued through the fall and, together with fraud at the polls, resulted in white Democrats regaining control of the state legislature and, in 1876, the governor's seat.

This political shift signaled the end of the Reconstruction era, confirmed when the federal government withdrew remaining troops in 1877.

The German soldiers provided the labor to build a replica model of the Mississippi River Basin for the U.S. Army Corps of Engineers, used for planning and designing flood prevention.

The financial dealings resulted in fraud-related convictions of Bernard Ebbers, CEO, and Scott Sullivan, CFO.

The company changed its name to MCI and moved its corporate headquarters location to Ashburn, Virginia.

As of July 3, 2017, Philip R. Fisher, a retired major general in the Mississippi National Guard,[16] is the city's mayor.

[18][19] Automotive component manufacturer Delphi Corporation operated a plant in Clinton from the early 1970s until its closure in 2009, making cable and wiring connectors.

[22] In 2018 the Clinton city government, citing problems with the sanitary condition, closed the library.