U.S. Route 259 is a north–south spur of U.S. Route 59 that runs for 250 miles (402 km) through rural areas of southeast Oklahoma and northeast Texas.

The highway's northern terminus is in the Ouachita Mountains, about 15 miles (24 km) south of Heavener, Oklahoma, where it branches off of its parent route, U.S. 59. The southern terminus is near Nacogdoches, Texas, where it reunites with U.S. 59. For most of its length, US 259 lies 30–50 miles to the west of its parent route.

US 259 begins at an intersection with its parent, US 59, on the north side of Nacogdoches, Texas. The highway continues due north, passing through Mount Enterprise, and around the eastern side of Henderson and Kilgore. 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. The highway continues due north, crossing Interstate 30 in northern Morris County, and crossing into Oklahoma in northwest Bowie County.

After crossing into McCurtain County, Oklahoma, US-259 immediately meets up with 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, and ODOT signage does not reflect a concurrency.

US-259 bypasses Idabel to the south and east, concurring with U.S. Highway 70 Bypass. East of Idabel, the bypass route ends, and US-259 begins a concurrency with mainline US-70 and SH-3. The three highways continue north to Broken Bow, where US-70 splits to the east toward DeQueen, Arkansas and SH-3 splits to the west, bound for Antlers. US-259 continues north alone, taking a winding path through the Ouachita Mountains of southeastern Oklahoma. The route passes Broken Bow Lake on its west side, with State Highway 259A serving as an access loop to the lake and Beavers Bend State Resort. Near the lake, US-259 crosses through the Ouachita National Forest for the first time. Near Smithville, the highway serves as the western terminus of State Highway 4.

North of the SH-4 junction, US-259 crosses into Le Flore County. The U.S. route then serves as the eastern terminus of SH-144 near Octavia. US-259 reenters the National Forest north of this junction, and intersects SH-63 at Big Cedar. It then has a junction with SH-1, the Talimena Drive. The highway reunites with US-59 about 10 miles (16 km) south of Heavener, reaching its northern terminus.

In Texas, the highway was designated in 1962 and assumed the entire route of the State Highway 26, which was then cancelled.

In Kilgore, Texas, US 259 is known as the Charles K. Devall Memorial Highway, as named by the Texas legislature

Prior to 1985, US 259 between Kilgore and Longview followed the current route of Texas State Highway 31. It entered Longview from the SW at the intersection of South St. and Spur 63. It then followed Spur 63 to US 80. US 259 then ran concurrently with US 80 to Eastman Rd. At the US 80/Eastman Rd. intersection, it reunited with the current route of US 259. In 1985, US 259 was rerouted to its current route along Interstate 20 to Eastman Rd, along the eastern edge of Longview, bypassing the central business district.

US-259 has one Business route in Texas. In 2006, a new bypass was completed around the eastern side of Kilgore. The bypass had been proposed as early as 1965, but funding did not become available until the late 1990s. The new bypass was designated as US-259, while the previous route through the Kilgore business district was designated as a business route. The new business route was approved by the AASHO in September 2006.

Formerly, US-259 continued into downtown Idabel, and the southeast portion of the Idabel bypass was double-designated as US-70 Bypass and US-259 Bypass. On 6 March 2000, the bypass route was decommissioned, and mainline US-259 was moved onto the bypass. However, as of 2008[update], some bypass signage is still in place, including signage indicating the former terminus of Bypass US-259 at US-70/SH-3.

SH-259A is a 10-mile (16 km) loop to Broken Bow Lake and Beavers Bend Resort Park north of Broken Bow, Oklahoma. It lies partially in the Ouachita National Forest and is occasionally signed as a U.S. highway.