The area known as St. Charles was within the territory of the Middle Mississippian culture during the Woodland Period of Native American History.

In early modern times, possibly after Hernando De Soto's initial exploration of the American Southeast, the area encompassing the whole of Arkansas County and much of Eastern Arkansas became Quapaw territory and remained so until the arrival of French explorers in the 17th century.

On June 17, 1862, at the Battle of Saint Charles, eight Federal vessels including the ironclad gunboat USS Mound City attempted to pass Confederate shore guns here, on the banks of the White River.

A single shot from a Confederate cannon entered the Mound City and penetrated her steam drum.

The resulting explosion and release of scalding steam killed most of her crew, approximately 129 men.

Most commerce of inland communities passed through the town, until rails reached DeWitt (Arkansas County), after which St. Charles began declining.

For many years, its economy depended on timber, fishing, hunting, trapping, mussels for the button industry, and crops.

The two men began to fight, and a local police officer arrested Griffin for assault, telling him he would be hanged.

By March 23, 1904, white mobs on horseback were accosting black citizens on sight, shooting those who resisted.

Between sixty and seventy black men, women and children were driven from their homes and penned inside a warehouse.

They were marched to the high point on the highway between St. Charles and De Witt, made to stand in a line, then all six were shot dead.

They were Abe Bailey, Mack Baldwin, Will Baldwin, Garrett Flood, Randall Flood, Aaron Hinton, Will Madison, Charley Smith, Jim Smith, Perry Carter, Kellis Johnson, Henry Griffin, and Walker Griffin.

To this day it remains little known, but in fact it was one of the largest murders of this sort, given the population of the town at the time, in Arkansas history.

The purpose of this expansion would be to protect wildlife that lives on the lower river and it would also preserve the Arkansas "Big Woods", which only 10% remains.

The climate in this area is characterized by hot, humid summers and generally mild to cool winters.