The highway is divided into two segments which combine for a length of 37.49 miles (60.33 km).

The western segment of Nebraska Highway 59 has a western terminus at Nebraska Highway 14 west of Creighton and an eastern terminus at U.S. Highway 81 northeast of Magnet.

It continues east into farmland and through Creighton, then intersects Nebraska Highway 13.

It continues due east and intersects Nebraska Highway 121 south of Wausa before ending northeast of Magnet at U.S. Highway 81.

[1][2] The eastern segment of Nebraska Highway 59 begins at Nebraska Highway 57 south of Coleridge and north of Belden.