Cross County was incorporated November 15, 1862. It was formed from St. Francis, Poinsett and Crittenden counties. It was named for Col. David C. Cross who came to the area in the 1840's. Eventually he was to own 85,000 acres of land making him a wealthy man and the most extensive landowner in the County. Col. Cross died at the home of his friend, William Ferry Wilkins, August 21, 1874 and is buried in the Wilkins Family Cemetery three miles south of Wynne.

There have been five county seats. Wittsburg was designated the first county seat in the act of incorporation, but due to union forces patrolling the area during the civil war county business could not be conducted there so three location commissioners were chosen to decide where the county seat should be located. They chose Pineville April 18, 1863. Dr. B. D. McClaran, the first county clerk, lived near Pineville. As no courthouse was erected, the county's business was conducted in his home.

The civil war was over in May 1865. Commissioners met at Pineville and selected the town of Cleburne as the next county seat. Cleburne, named after Patrick R. Cleburne, a Confederate general from Helena who had been Col. Cross's commander in the civil war, was located in the center of the county. Col. Cross deeded the center block in the town containing 3/5 acre to the county on which to build a courthouse. His residence on the site was used as a temporary courthouse. The seat of justice was there from 1865 to 1868.

As early as 1866 petitions had been circulated asking that the seat be changed to Wittsburg. In June 1868 three locating commissioners were elected and in October 1868 they selected Wittsburg, by now a thriving river port, as the next county seat. It was there from October 1868 to 1884.

In 1882 when the Helena branch of the Iron Mountain and Southern Railroad was completed, Wittsburg began to decline. Steam trains were replacing steamboats. Many business and professional people were moving to Vanndale, which was located on the new railroad. An election was held and in 1884 Vanndale was declared the next county seat. The first courthouse was built there in 1888.

Meanwhile, the town of Wynne south of Vanndale was growing. Wynne started in 1882 when a train derailed leaving one boxcar without wheels and off the track. The car was placed upright and designated Wynne station in compliment to Capt. Jesse Watkins Wynne, a prominent businessman and banker of Forrest City. Wynne was formally incorporated May 28, 1888. In July 1903 a petition was presented to the county court asking that an election be held to move the county seat from Vanndale to Wynne. Wynne won the election and has remained the county seat.