The 2nd Maryland Infantry was an American military regiment in the Union Army during the American Civil War. It should not be confused with the 2nd Maryland Infantry, CSA, which was composed of Maryland volunteers who fought for the Confederacy during the war. The regiment fought at numerous battles during the course of the war, and lost 5 officers and 84 men killed and wounded, plus 3 officers and 134 men died of disease, for a total of 226 casualties.

The Battle of Antietam, also called the Battle of Sharpsburg, particularly in the Southern United States, took place during the American Civil War on September 17, 1862, between Confederate General Robert E. Lee's Army of Northern Virginia and Union Major General George B. McClellan's Army of the Potomac near Sharpsburg, Maryland, and Antietam Creek. Part of the Maryland Campaign, it was the first field army–level engagement in the Eastern Theater of the American Civil War to take place on Union soil. It remains the bloodiest day in American history, with a tally of 22,727 dead, wounded, or missing on both sides. Although the Union Army suffered heavier casualties than the Confederates, the battle was a major turning point in the Union's favor.