The northeastern counties of South Carolina compose the Pee Dee region of the state.

There are numerous boat landings, yet most of the river is wild, with forests of tupelo, oak and gum along its shores.

The first Europeans believed to have possibly navigated part of the river was a party sent by Lucas Vázquez de Ayllón in 1521.

The world's largest lumber company existed at the turn of the 20th century near the river's mouth at Georgetown.

The virgin pine forests of the Pee Dee region were cutover, and the logs floated in rafts downriver to be sawn into lumber and exported to the northern United States and Europe.

Rice culture declined with the freedom of slave labor after the Civil War and with increased overseas competition.