There are two major sites related to the Civil War on the Mississippi Gulf Coast. Fort Massachusetts is a well-preserved brick fortification on Ship Island that was once part of the coastal defenses of the United States. The unfinished fort was abandoned by Confederate forces in 1861. Afterward Ship Island was occupied by Union troops for the remainder of the war and the U.S. Army Corps of Engineers returned to resume fort construction. In 1862, Ship Island was used by the Union fleet under the command of Admiral David Farragut as a staging area for the capture of Mobile and New Orleans. In addition to the fort and its garrison, portions of Ship Island were used during the Civil War for holding prisoners of war and as a base for an African-American regiment of the Louisiana Native Guards.

The other prominent site on the Mississippi Coast related to the Civil War is Beauvoir, the last home of Jefferson Davis, the only president of the Confederate States of America. Although Davis lived at Beauvoir after the Civil War, much of the interpretation at the site is devoted to the Confederacy and Davis's role as its leader. Also, a cemetery located on the grounds is the resting place of hundreds of veterans of the Confederate Army, including the Tomb of the Unknown Confederate Soldier.