The slow-moving waters of the Okefenokee are tea-colored due to the tannic acid released from decaying vegetation. The principal outlet of the swamp, the Suwannee River, originates in the heart of the Okefenokee and drains southwest into the Gulf of Mexico. The swamp's southeastern drainage, to the Atlantic Ocean, is the St. Mary's River, which forms the boundary between Georgia and Florida.

Okefenokee National Wildlife Refuge was established in 1937 in order to preserve much of the 438,000-acre area of the Okefenokee Swamp. Currently the refuge boundaries encompass roughly 396,000 acres. In 1974, to further ensure the protection of this unique ecosystem, the interior 353,981 acres of the refuge were designated a National Wilderness Area.