For most of its length, the Antoine River crosses the Athens Piedmont Plateau, a series of east–west ridges that serve as the foothills of the Ouachita Mountains.

The Antoine River is notable for rapid changes in water level after rains.

It is primarily a clear and rocky stream, the last free-flowing river of any size in the Athens Plateau that has not been dammed.

Most tributaries of the Antoine River are small rocky streams that flow in from the west.

The largest tributary of the Antoine River is Wolf Creek in southern Pike County.