Cairo is located at the confluence of the Mississippi and Ohio Rivers. The rivers converge at Fort Defiance State Park, a Civil War fort that was commanded by General Ulysses S. Grant. Cairo has the lowest elevation of any location within Illinois and is the only city in the state surrounded by levees. This part of Illinois is known as Little Egypt.
Several blocks in the town comprise the Cairo Historic District, listed on the National Register of Historic Places (NRHP). The Old Customs House is also on the NRHP. The city is part of the Cape Girardeau−Jackson, MO-IL Metropolitan Statistical Area. The population at the 2010 census was 2,831, a significant decline from its peak population of 15,203 in 1920.
The entire city was evacuated during the 2011 Mississippi River Floods, after the Ohio River rose above the 1937 flood levels, out of fear of a 15-foot wall of water inundating the city. The United States Army Corps of Engineers breached levees in the Mississippi flood zone below Cairo in Missouri in order to save the areas above the breach along both the Ohio and Mississippi rivers.