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It is formed at Louisa, Kentucky by the confluence of the Tug Fork and Levisa Fork. It flows generally north in a highly meandering course. It joins the Ohio at Catlettsburg, Kentucky, 8 mi (13 km) west of Huntington, West Virginia, at the common boundary between West Virginia, Kentucky, and Ohio.
The river is navigable and carries commercial shipping, primarily coal mined in the nearby region.
The name of the river comes from the presence of extensive sand bars. The Native American names for the river included Tatteroi, Chatteroi, and Chatterwha which had similar meaning to the English name. It was known to the Lenape as Sikeacepe, meaning "Salt River", from the presence of salt lick s on the river (see: Licking River).