In 1794, President George Washington received congressional approval to establish armories and arsenals throughout the young nation. The second site selected was Harpers Ferry. Located at the confluence of the Potomac and Shenandoah rivers, the village had abundant water power and was only 62 miles from the national capital at Washington. From 1800 to 1861, the arsenal produced 620,000 shoulder-arms and became the largest installation of its kind in the South.

Three times in the Civil War era Harpers Ferry was the scene of major national events. In 1859, abolitionist John Brown momentarily seized the arsenal in an unsuccessful attempt to start a slave insurrection. On April 18, 1861, the day following Virginia secession, several companies of state militia closed in on the 47 army regulars defending the arsenal. The Union soldiers set fire to the buildings and fled. The Virginians reacted quickly and saved most of the machinery. For a time, Harpers Ferry was the northernmost point of the Southern Confederacy.

The town changed hands eight times during the Civil War. The most spectacular of those campaigns occurred September 14-15, 1862, when Confederate Gen. Thomas J. "Stonewall" Jackson forced the surrender of a large Union garrison inside the town. The 12,500 prisoners taken by Jackson was the largest capitulation of federal troops in the war.

For most of the conflict, looters and guerrillas reduced Harpers Ferry to a no man's land, only a shadow of its former self. Artillery fire shattered homes and buildings; streets became avenues of accumulated trash; the vital railroad bridge across the Potomac was destroyed and rebuilt nine times. An 1865 visitor stated that "all about the town are rubbish, filth, and stench." However, like so many other communities, Harpers Ferry would rise from the ashes of war.