Its northern terminus is in the Ouachita Mountains, approximately 15 miles (24 km) south of Heavener, Oklahoma, where it reunites with US 59.

The highway continues due north, passing through Mount Enterprise, and around the eastern side of Henderson and Kilgore.

[2] It then has a concurrency with Interstate 20 of about 6 miles (9.7 km), then continues north around the eastern edge of Longview along Eastman Rd.

After crossing into McCurtain County, Oklahoma, US-259 immediately meets State Highway 87, and continues north through Harris.

Maps indicate that US-259 and SH-87 overlap to Idabel, but officially, this is not the case,[3] and ODOT signage does not reflect a concurrency.

US-259 continues north alone, taking a winding path through the Ouachita Mountains of southeastern Oklahoma.

The highway reunites with US-59 about 10 miles (16 km) south of Heavener, reaching its northern terminus.

In 1985, US 259 was rerouted to its current route along Interstate 20 to Eastman Road, then left to go north, along the eastern edge of Longview, bypassing the central business district.