Cairo is the southernmost city in Illinois and the county seat of Alexander County.
The city is located at the confluence of the Ohio and Mississippi rivers. Fort Defiance, a Civil War camp, was built at the confluence in 1862 by Union General Ulysses S. Grant to control strategic access to the river. Cairo has the lowest elevation of any location in Illinois and is the only Illinois city to be surrounded by levees. It is in the area of Southern Illinois known as Little Egypt.
Several blocks in the town comprise the Cairo Historic District, listed on the National Register of Historic Places. The Old Customs House is also on the NRHP. The city is part of the Cape Girardeau–Jackson, MO–IL Metropolitan Statistical Area. Being bypassed by transportation changes and industrial restructuring cost many jobs: the population at the 2010 census was 2,831. The city's peak population was 15,203 in 1920.
The entire city was evacuated during the 2011 Mississippi River Floods, after the Ohio River rose higher than the 1937 flood levels, with the possibility of 15 feet of water inundating Cairo.