The Cheraw and Pee Dee Indians were the earliest known inhabitants of what is now Chesterfield County. Of Siouan stock, the Cheraws were the dominant tribe in the upper Pee Dee. They reached the height of their power around 1650 and maintained a well-fortified village on the river hill close to present day Cheraw. Disease greatly decimated their population after a time, and they joined the Catawba Confederacy, leaving only their names, well established trading routes, and by the time of the Revolution, a few scattered families.

Most of Cheraw's early settlers were English, Scots, French or Irish. Two of the earliest of these were James Gillespie and Thomas Ellerbe who started a trading center and water mill at the Cheraw Hills around 1740. Welsh Baptists later made their way up river, too. By 1750 Cheraw was one of six places in South Carolina appearing on English maps and was an established village with a growing river trade. Joseph and Eli Kershaw came to the area in 1750 and were later granted part of the present town of Cheraw. They formally laid out the street system with broad streets and a town green. By 1830, the streets were lined with triple rows of elm trees. Some of the median trees remain, particularly on Third Street, but many were removed at the turn of the century to put in water lines.

The Kershaws called the town "Chatham" after the Earl of Chatham, William Pitt, but this never seemed to have had wide acceptance, and Cheraw or Cheraw Hill continued to be used interchangeably with Chatham. Cheraw has been the official name since the town's incorporation in 1820.

During the Revolution, Cheraw was the center of much unrest sometimes being held by the British and sometimes by the patriots. Gen. Greene's army had a camp of repose just across the river, and St. David's church was used by both armies as a hospital.

Cheraw was the head of navigable waters on the Great Pee Dee and was thus the shipping center for a wide area. Corn, tobacco, rice and indigo were grown in the more fertile surrounding lands and cattle raising, with related tanning and curing industries, was a major source of income. Prior to the Confederate War, both the largest cotton market between Georgetown and Wilmington, and the largest bank in South Carolina outside of Charleston were located here.

The first bridge across the Pee Dee and the advent of steamship service to Cheraw in the 1820's led to a golden age, and numerous buildings from this period still grace Cheraw's streets. A serious fire destroyed most of the business district in the 1835, but by the end of the 1850's Cheraw was a prosperous, secure town, which served as a regional center of business, education, culture and religion.

Citizens of Cheraw played a leading role in South Carolina's secession, and the town became a haven for refugees and a storage place for valuables and military stores during the Confederate War. In March of 1865, Cheraw played unwilling host to more of Gen. William T Sherman's Union troops than any other South Carolina city. They found Cheraw "a pleasant town and an old one with the southern aristocratic bearing", and amazingly they left it that way. Although the business district was destroyed in an accidental explosion, no public buildings or dwellings were burned. However, the County Courthouse in Chesterfield was burned and exact dates on many Cheraw buildings are unknown.

Prosperity began to return by 1900 and many fine Victorian and Revival buildings are still in evidence here. Cheraw in the 1960's began to diversify her industrial base, and today Cheraw is a prosperous town that takes pride in preserving her past while planning for the future.