The Santa Fe Swamp is 95-percent floodplain 7,046-acre (28.5 km²) swamp. Along with Lake Santa Fe and Little Lake Santa Fe, it serves as headwaters of the Santa Fe River, which drains into the Suwannee River and then finally the Gulf of Mexico. It is located to the north of those lakes in Alachua County, Florida.

The 5,356-acre (21.7 km²) Santa Fe Swamp Wildlife and Environmental Area (WEA) was donated to the Suwannee River Water Management District in 1984 by Georgia-Pacific Corporation. At that time, it was the largest and most environmentally significant donation in the state of Florida's history.