From its source in Polk County, Arkansas, it flows approximately 177 miles (285 km)[3] to its confluence with the Red River at Hugo, Oklahoma.

[4] Muriel H. Wright suggested that Kaimichi may be from the French word kamichi, which meant "horned screamer", and possibly referred to the whooping cranes along the river.

At Antlers the river meets the massive geological formation known as Standpipe Hill, forcing its turn to the southeast.

Additional, smaller dams have impounded the waters of the tributaries over time, mostly for the purpose of powering sawmills and other light, localized industry.

The powerful Caddoan Mississippian culture based at Spiro Mounds held sway over the Kiamichi River valley, which formed a part of its trade network.

A prehistoric fish weir, or trap, in the river in Pushmataha County, excavated by the Oklahoma Archeological Survey, is a particularly revealing site.

Nuttall and Long were the precursors of empire; the region was actively settled by Choctaw Indians displaced from elsewhere in the United States starting in 1832.

[8] After the relocation of the Choctaw Nation to the Indian Territory in 1832, the river defined the political boundary or border between counties and districts.

Forming an easily recognizable geographic frontier, it served in this capacity until Oklahoma's statehood in 1907, when the Choctaw Nation ceased to exist and its political subdivisions were eliminated.

In 1825 the Arkansas legislature petitioned the United States Congress to remove the Great Raft, as the logjam was called, so that boats could ply the Red River as far west as the mouth of the Kiamichi and the newly established Fort Towson.

[10] Security along the Red River, the United States' (US) international frontier with the Spanish Empire was a concern, and the US established a chain of forts along the border.

Transportation in the Kiamichi River valley was revolutionized between 1882 and 1887 with the construction of the St. Louis and San Francisco Railroad, commonly known as the Frisco.

Part of a national network connecting Fort Smith, Arkansas with Paris, Texas, the railway was constructed parallel to the Kiamichi River from Talihina to Kellond, a small settlement three miles north of Antlers, Oklahoma.

During World War II, a training flight conducted by Britain's Royal Air Force—flying from a base in Texas—went awry in poor weather and two planes crashed.

[12] On October 29, 1961, President John F. Kennedy visited Big Cedar, east of Talihina, Oklahoma to give a speech marking the opening of U.S. Route 259.

[13] In August 1975 the Kiamichi River made national news when its bottomlands were the scene of a days-long hunt for two elephants that had escaped from a circus in Hugo, Oklahoma.

American Whitewater, a private organization, defines seven miles of the river near Big Cedar as a "Class II-III rapid".

[15] Three federally designated endangered species occupy the river valley – the Indiana bat, red-cockaded woodpecker and leopard darter.

The Kiamichi River has been studied since at least 1894, when the first scientific fish collection was made at Walnut Creek at Albion, Oklahoma.