Cairo, Illinois in the context of Coterminous municipality

The Ohio River (Seneca: Ohi:yo') is a 981-mile-long (1,579 km) river in the United States. It is located at the boundary of the Midwestern and Southern United States, flowing in a southwesterly direction from Pittsburgh, Pennsylvania, to its mouth on the Mississippi River in Cairo, Illinois. It is the third largest river by discharge volume in the United States and the largest tributary by volume of the Mississippi River. It is also the sixth oldest river on the North American continent. The river flows through or along the border of six states, and its drainage basin includes parts of 14 states. Through its largest tributary, the Tennessee River, the basin includes several states of the southeastern United States. It is the source of drinking water for five million people.

The river became a primary transportation route for pioneers during the westward expansion of the early U.S. The lower Ohio River just below Louisville was obstructed by rapids known as the Falls of the Ohio where the elevation falls 26 feet (7.9 m) in 2 miles (3.2 km) restricting larger commercial navigation, although in the 18th and early 19th century its three deepest channels could be traversed by a wide variety of craft then in use. In 1830, the Louisville and Portland Canal (now the McAlpine Locks and Dam) bypassed the rapids, allowing even larger commercial and modern navigation from the Forks of the Ohio at Pittsburgh to the Port of New Orleans at the mouth of the Mississippi on the Gulf of Mexico. Since the "canalization" of the river in 1929, the Ohio has not been a natural free-flowing river; today, it is divided into 21 discrete pools or reservoirs by 20 locks and dams for navigation and power generation.

The Mississippi embayment is a physiographic feature in the south-central United States, part of the Mississippi Alluvial Plain. It is essentially a northward continuation of the fluvial sediments of the Mississippi River Delta to its confluence with the Ohio River at Cairo, Illinois. The current sedimentary area was formed in the Cretaceous and early Cenozoic by the filling with sediment of a pre-existing basin. An explanation for the embayment's formation was put forward by Van Arsdale and Cox in 2007: movement of the Earth's crust brought this region over a volcanic "hotspot" in the Earth's mantle causing an upthrust of magma which formed the Appalachian-Ouachita range. Subsequent erosion caused a deep trough that was flooded by the Gulf of Mexico and eventually filled with sediment from the Mississippi River.

Alexander County is the southernmost county in the U.S. state of Illinois. As of the 2020 census, the population was 5,240. Its county seat is Cairo and its western boundary is formed by the Mississippi River.

Alexander County is part of the Cape Girardeau–Jackson metropolitan area which is made up of jurisdictions on both sides of the Mississippi River.

Cairo Precinct is located in Alexander County, Illinois, United States. As of the 2020 census, its population was 1,733. The precinct is coterminous with the city of Cairo.

Fort Defiance, known as Camp Defiance during the American Civil War, is a former military fortification located at the confluence of the Ohio and Mississippi rivers in the city limits of Cairo, in Alexander County, Illinois. The strategic significance of the site has been known since prehistoric times with archaeological evidence of warfare dating to the Mississippian era. It is the southernmost park in the state of Illinois. At 279 feet (85 m) in elevation, Fort Defiance Point is also Illinois' lowest point.

Formerly a state park, it has been owned and maintained by the city of Cairo since the 1990s. The Illinois Department of Natural Resources assumed control of Fort Defiance on July 31, 2014, with the goal of returning it to state park status. The park is a satellite of Horseshoe Lake State Fish and Wildlife Area.

The Mississippi River campaigns, within the Western andTrans-Mississippi Theater of the American Civil War, were a series of military actions by the Union Army during which Union troops, helped by Union Navy gunboats and river ironclads, took control of the Cumberland River, the Tennessee River, and the Mississippi River, a main north-south avenue of transport.

The campaign on and along the Mississippi River started in February 1862 with Union forces pushing down from Cairo, Illinois into disputed territory in Missouri and Kentucky and Confederate territory in Tennessee. It ended with the surrender of the last Confederate strongholds on the Mississippi River, Vicksburg, Mississippi on July 4, 1863 and of Port Hudson, Louisiana on July 9, 1863. Flag Officer Foote initially commanded the Union naval forces, which were later led by Farragut and Porter. Union ground forces were primarily under the command of General Grant.