The lower part of the river flood plain was extensively developed for rice culture in colonial time, as rice was a major export of the area from the port at Georgetown. Rice culture declined with the loss of slave labor after the Civil War, and increased competition. Two hurricanes at the beginning of the 20th century destroyed much of the canal work and effectively ended the remnants of rice culture.
Today the river is not extensively used for navigation. It is an important source of electric power and public water supplies, as well as recreational use. While the Pee Dee is free-flowing in South Carolina, upstream in North Carolina several dams have been constructed on it. The opening and closing of these dams causes dramatic swings in the depth of the river in South Carolina. The sharing of water between the two states has sometimes been a matter of controversy, particularly during period of drought. Some commercial fishing is done during the winter shad run, and for shrimp in the lower reaches. The river is excellent for recreational fishing and boating. There are numerous boat landings, yet most of the river is wild, with forests of tupelo, oak and gum along its shores. Herons and alligators can be seen along the way, and a lucky sighting of a bald eagle is possible.