The Altamaha River flows through a flood plain up to five miles (8.0 km) wide, consisting of some of the last remaining hardwood bottomlands and cypress swamps in the American South.

[3] The unusual Franklin tree (Franklinia alatamaha), now extinct in the wild, was found by John Bartram along the Altamaha River in 1765.

[7] In prehistoric times, the Timucua people occupied northern Florida and a portion of Georgia reaching as far north as the Altamaha River.

Fort Caroline, built by the French in 1564 and probably the oldest European fortified settlement in North America, was likely constructed near the mouth of the Altamaha River.

Historian Fletcher Crowe noted: “This fort is older than St. Augustine, considered to be the oldest continuously inhabited city in America."

In 1565, Spanish soldiers under Pedro Menéndez marched into Fort Caroline and slaughtered all the French Huguenot Protestants, regardless of age or gender (some 143 men and women) residing there.

For centuries, riverboats used the Altamaha as the main transportation route to reach those towns and the plantations founded along the river.

Among the many "riverman monikers" was Old Hell Bight, where the river marks the border between Long County to the north and Wayne County to the south, and is a particularly troublesome bend, with associated dangerous currents, where a pilot and crew might lose "their wages, their timber, and occasionally their lives"[14][15][16] The timber rafts had a maximum width of about forty feet (12 m), that being the widest that could pass between the pilings of railroad bridges.

To distant climes, a dreary scene, Where half the convex world intrudes between, Through torrid tracts with fainting steps they go, Where wild Altama murmurs to their woe.

Far different there from all that charm'd before, The various terrors of that horrid shore; Those blazing suns that dart a downward ray, And fiercely shed intolerable day; Those matted woods where birds forget to sing, But silent bats in drowsy clusters cling; Those poisonous fields with rank luxuriance crowned, Where the dark scorpion gathers death around; Where at each step the stranger fears to wake The rattling terrors of the vengeful snake; Where crouching tigers wait their hapless prey, And savage men, more murderous still than they; While oft in whirls the mad tornado flies, Mingling the ravaged landscape with the skies.

[18] A Rayonier paper mill that manufactures cellulose fibers used in plastics and absorbent materials for diapers, tampons, and other products is located on the southern bank of the Altamaha River in Wayne County.

[citation needed] In January 2021, Ingka Investments, part of the parent company of IKEA, acquired 10,840 acres (4,390 hectares) near the Altamaha River Basin from The Conservation Fund.

The legal agreement is to protect the land from fragmentation, restore the longleaf pine forest, and safe-guard the habitat of the gopher tortoise.”[19][20]