The Ozark Highlands Scenic Byway includes 35 miles of Arkansas State Scenic Highway 21 from the Ozark National Forest southern boundary north of Clarksville in Johnson County to the northern boundary near the Upper Buffalo Wilderness and Buffalo National River in Newton County. Arkansas State Highway 16 from Fallsville to Edwards Junction in Newton County joins this route for eight and one half miles. This is truly a “highlands route,” traversing ridges between headwaters of the major streams.

It serves as a major travel way for residents, visitors and commercial vehicles traveling north from Clarksville to historically major recreation areas and resorts, centers of commerce and points of local interest. Chief among these are the Arkansas communities of Harrison, Jasper, Berryville, Eureka Springs, The Ozark National Forest, The Ozark Highlands Trail, Buffalo North River and the White River and its tributaries. This is also a major route of travel from the Interstate highway system to Missouri and points north.

The outstanding characteristics of this highway are panoramic views, colorful flora, and rugged terrain. Wildlife is abundant and it is not uncommon to see white-tail deer, wild turkey, and black bear, as well as smaller species such as songbirds and squirrels. Occasionally, bald eagles and golden eagles are also seen. Located on the byway is Ozone Recreation Area. Significant landmarks include the escarpment overlook of the Arkansas River Valley, the settlements of Ozone, Salus, Fallsville, Edward's Junction and Mossville.