U.S. Route 259 is a north–south spur of U.S. Route 59 that runs for 250 miles (400 km) through rural areas of northeastern Texas and southeastern Oklahoma. The highway's southern terminus is near Nacogdoches, Texas, at an interchange with its parent route, US 59. Its northern terminus is in the Ouachita Mountains, approximately 15 miles (24 km) south of Heavener, Oklahoma, where it reunites with US 59. For most of its length, US 259 lies 30–50 miles (48–80 km) to the west of its parent route.

U.S. Route 59 is a north–south United States highway. A latecomer to the U.S. numbered route system, US 59 is now a border-to-border route, part of the NAFTA Corridor Highway System. It parallels U.S. Route 75 for nearly its entire route, never much more than 100 miles (160 km) away, until it veers southwest in Houston, Texas. Its number is out of place since US 59 is either concurrent with or entirely west of U.S. Route 71. The highway's northern terminus is 9 mi (14 km) north of Lancaster, Minnesota, at the Lancaster–Tolstoi Border Crossing on the Canada–US border, where it continues as Manitoba Highway 59. Its southern terminus is at the Mexico–US border in Laredo, Texas, where it continues as Mexican Federal Highway 85D.