The National Audubon Society accepted responsibility for management and started constructing the first boardwalk through the swamp in 1955.

In all, nearly 45 km2 (17 sq mi) of wetland was purchased or donated, most of it from or by the owners, Lee Tidewater Cypress Center Co. and Collier Enterprises.

[2] In 2018, researchers at the Sanctuary determined that beginning around the year 2000, the amount of groundwater in the park began to diminish.

Records have been kept of water levels beginning in 1957, and analysis determined that previous changes in the landscape – such as the building of Immokalee Road, the use of canals to drain land for real estate development, the increase in agriculture in the area, the installation of electrical and telephone lines, or the paving over of neighboring wetlands – had not altered the water levels, which are measured at Lettuce Lake, the park's deepest standing water.

Specialist birds include limpkin, barred owl and, in summer, swallow-tailed kite.