The Buffalo River is one of the few remaining unpolluted, free-flowing rivers in the lower 48 states offering both swift-running and placid stretches. The Buffalo National River encompasses 135 miles of the 150-mile long river. It begins as a trickle in the Boston Mountains 15 miles above the park boundary. Following what is likely an ancient riverbed, the Buffalo cuts its way through massive limestone bluffs traveling eastward through the Ozarks and into the White River. The national river has three designated wilderness areas within its boundaries.

Headquarters is located in Harrison, Arkansas, providing administrative services to the national river. The Tyler Bend Visitor Center, the main visitor center for the park, is located eleven miles north of Marshall, Arkansas. The park has two other visitor contact stations; the Pruitt Ranger Station, located five miles north of Jasper, Arkansas on Highway 7, and Buffalo Point Ranger Station, located 17 miles south of Yellville, Arkansas, on Highway 14.