The North Fork of the Red River rises in central western Gray County (at 35°24' N, 101°05' W) and flows east for seventy miles across Gray and Wheeler counties. It is joined by McClellan Creek, its chief tributary, just west of the Wheeler county line. The stream crosses the 100th meridian into Oklahoma and flows east across Beckham County and then southeast to form the county lines between Greer and Kiowa, Kiowa and Jackson, and Jackson and Tillman counties. It joins the Prairie Dog Town Fork of the Red River to form the Red River proper on the Oklahoma-Texas boundary northeast of Vernon, in Wilbarger County (at 34°19' N, 99°12' W). The basin is characterized by mostly flat terrain with local shallow depressions and clay loam and sandy loam soils. Vegetation consists primarily of water-tolerant hardwoods and grasses.
The upper North Fork was the scene of much activity during the Indian wars of the 1870s. On September 29, 1872, Col. Ranald S. Mackenzie mounted his successful attack against Mow-way's Comanche village on the North Fork east of the site of present Lefors. Col. John W. Davidson campaigned successfully against the Cheyennes along the stream during the Red River War in the fall of 1874. For years, beginning with the Adams-Onís Treaty of 1819, the North Fork was erroneously believed to be the Red River's main tributary; for that reason Texas claimed Greer County until 1896, when it was allotted to Oklahoma.