The river had great significance in the history of the Native Americans. It was a primary transportation route during the westward expansion of the early U.S. It flows through or along the border of six states, and its drainage basin encompasses 14 states, including many of the states of the southeastern U.S. through its largest tributary, the Tennessee River. During the nineteenth century, it was the southern boundary of the Northwest Territory, thus serving as the border between free and slave territory. It is sometimes referred to as the "Mason-Dixon line" as it is commonly acknowledged as the western natural extension of the original Mason-Dixon line that divided Pennsylvania and Delaware from Maryland and West Virginia (then a part of Virginia) thus being the unofficial, and at times disputed, border between the Northern United States and the American South or upland South.
The Ohio River is a climatic transition area as its water runs along the periphery of the humid subtropical climate and humid continental climate thereby being inhabited by fauna and flora of both climates. In his Notes on the State of Virginia published in 1781-82, Thomas Jefferson stated: "The Ohio is the most beautiful river on earth. Its current gentle, waters clear, and bosom smooth and unbroken by rocks and rapids, a single instance only excepted.
The river then follows a roughly southwest and then west-northwest course before bending to a west-southwest course for most of its length. It flows along the borders of West Virginia, Ohio, Kentucky, Indiana, and Illinois, until it joins the Mississippi near the city of Cairo, Illinois.
Major tributaries of the river, indicated by the location of their mouth, include:
Many small rivers were altered or abandoned after the upper Ohio River formed. Valleys of some abandoned rivers can still be seen on satellite and aerial images of the hills of Ohio and West Virginia between Marietta, Ohio, and Huntington, West Virginia. As testimony to the major changes that occurred, the valleys are actually found on hilltops.
On May 19, 1749, King George II of Great Britain granted the Ohio Company a charter of land around the forks. Exploration of the territory and trade with the Indians in the region near the Forks by British colonials from both Pennsylvania and Virginia—both of whom claimed the territory—led to conflict with French forces that also claimed the region and had built forts along the Allegheny River. This directly led to the French and Indian War in North America. The French and Indian War was part of a more global conflict --perhaps the world's first truly global conflict --the Seven Years' War between England and France. After several initial defeats, the British eventually gained sovereignty over the Ohio Valley.
In 1774, the Quebec Act restored the land east of the Mississippi River and north of the Ohio River to Quebec, appeasing the French-speaking British subjects, but angering the 13 Colonies. They listed it as one of the Intolerable Acts, which precipitated the American Revolution.
Louisville, Kentucky was founded at the only major natural navigational barrier on the river, the Falls of the Ohio. The Falls were a series of rapids where the river dropped in a stretch of about . In this area the river flowed over hard, fossil-rich beds of limestone. The first locks on the river were built at Louisville to circumnavigate the falls. Today it is the site of McAlpine Locks and Dam.
Because the Ohio River flowed westwardly, it became the convenient means of westward movement by pioneers traveling from western Pennsylvania. After reaching the mouth of the Ohio, settlers would travel north on the Mississippi River to St. Louis, Missouri. There, some continued on up the Missouri River, some up the Mississippi, and some further west over land routes. In the early 19th century, pirates, such as Samuel Mason, settled at Cave-In-Rock, Illinois, waylaid travelers on their way down the river, killed them, stole their goods, and scuttled their boats. The folktales of Mike Fink recall the keelboats used for commerce in the early days of European settlement. In 1843 the Ohio river boatmen were the inspiration for Dan Emmett's The Boatman's Dance.
Other boats traveled south on the Mississippi to New Orleans and sometimes beyond to the Gulf of Mexico and other ports in the Americas and Europe. This provided a much needed route for goods from the west, since the trek east over the Appalachian Mountains was long and arduous. The need for access to the port of New Orleans by settlers in the Ohio Valley led to the Louisiana Purchase in 1803.
Because it is the Southern border of Ohio, Indiana and Illinois, the Ohio River was a part of the border that divided free states and slave states in the years before the American Civil War. The expression "sold down the river" originated as a lament of Kentucky slaves being split apart from their families and sold in Louisville and other Kentucky locations to be shipped via the Ohio River down to New Orleans to be sold yet again to owners of cotton and sugar field plantations. Before and during the Civil War, the Ohio River was called the "River Jordan" by slaves escaping to freedom in the North via the Underground Railroad. As depicted in several novels by Harriet Beecher Stowe and Toni Morrison. More routes, and more escaping slaves made their perilous journey north to freedom across the Ohio River, than anywhere else across the north-south frontier. In 1831, in the Ohio River town of Ripley, Ohio, an irate slave catcher, in hot pursuit, coined the term, 'Underground Railroad,' when his quarry apparently just vanished' in one. Ripley was a hotbed of abolitionist activity. Runaway slaves were generally welcomed there. And free-to-operate-in-the-north Slave Catchers also worked openly in Ripley. In Ripley, Eliza was the true life character, of Harriet Beecher Stowe's novel. Eliza and her baby, crossed the Ohio one winter night, slipping, and cutting her feet as she leaped from one ice floe to the next. Farther down the river, near Grandview, Indiana, slave Josiah Henson started his daring escape toward freedom with his entire family. Today, the Ohio River generally separates Midwestern Great Lakes states from Southern border states.
The charter for Virginia went not to the middle of the Ohio River but to its far shore, so that the entire river was included in the lands owned by Virginia. Therefore, where the river serves as a boundary between states, the entire river belongs to the states on the east and then the south, i.e., West Virginia and Kentucky, that were divided from Virginia. It is for that reason that Wheeling Island, the largest inhabited island in the Ohio River, belongs to West Virginia, even though it is much closer to the Ohio shore than to the West Virginia shore. Kentucky brought suit against Indiana in the early 1980s because of the building of the Marble Hill nuclear power plant in Indiana, which would have discharged its waste water into the river. The U.S. Supreme Court held that Kentucky's jurisdiction (and, implicitly, that of West Virginia) extended only to the low water mark of 1793 (important because the river has been extensively dammed for navigation, so that the present river bank is north of the old low water mark.) Similarly in the 1990s, Kentucky disputed Illinois' right to collect taxes on a riverboat casino docked in Metropolis, citing their control of the entire river. Aztar opened their own casino riverboat that docked in Evansville, Indiana at about the same time. Although cruises on the Ohio river were at first done in an oval pattern up and down the Ohio, the state of Kentucky soon protested and cruises were limited to going forwards then reversing and going backwards on the Indiana shore only.
In the early 1980s, the Falls of the Ohio National Wildlife Conservation Area was established at Clarksville, Indiana. In 2006, Cincinnati, Ohio, Indie rock band Nevada Smith published a bootleg version of their song "Il Fiume Fluisce Colore Maronne", a humorous protest song against the pollution in the Ohio. In 1993, Louisville band Love Jones released a song about recreational life on the Ohio River called "Ohio River".
While the Ohio River is quite deep, it is a naturally shallow river that was artificially deepened by series of dams. The dams raise the water level in shallow stretches, allowing for commercial navigation. Near its origin at the confluence of the Allegheny and Monongahela Rivers, the Ohio remains fairly shallow, never rising above around deep all the way past Cincinnati. From its origin to Cincinnati, the average depth is approximately . However, once past Cincinnati, the river deepens substantially. Due to the damming, along with glacier formations and migrations in the latter part of the second Ice Age, the river's depth increases nearly fivefold over about , coming to a maximum depth of just west of Louisville, Kentucky. The around Louisville represent the deepest area of the river with an average depth of approximately , allowing for much larger vessels to traverse the river. From Louisville, the river loses its depth very gradually until its confluence with the Mississippi at Cairo, Illinois, where it has an approximate depth of , because it is more free flowing. The natural depth of the river varies from about 3 feet to 40 feet.
Water levels for the Ohio River are predicted daily by the National Oceanic and Atmospheric Administration (NOAA). The water depth predictions are relative to each local flood plain based upon predicted rainfall in the Ohio River basin in five reports as follows: