The route begins at Highway 7 near Bergman and runs north to Bull Shoals Lake.

The route winds north through a sparsely populated area, passing through the unincorporated community of Boone.

A brief concurrency with Highway 14 begins in northern Boone County.

After the overlap, Highway 281 turns north and runs to Tucker Hollow Park on Bull Shoals Lake, where the route terminates.

Media related to Arkansas Highway 281 at Wikimedia Commons