The fort was occupied off and on for various military purposes from its completion until after World War I, when it served as a training station. It is now a National Historic Landmark and historical museum owned and operated by Plaquemines Parish.

Fort Jackson was the site of the Battle of Forts Jackson and St. Philip from April 16 to April 28, 1862, during the American Civil War. The Confederate-controlled fort was besieged for 12 days by the fleet of U.S. Navy Flag Officer David Farragut. Fort Jackson fell on April 28 after the Union fleet bombarded it and then sailed past its guns. A mutiny against the officers and conditions then occurred and the fort fell to the Union. Union forces then went on to capture New Orleans.

Following the engagement, Fort Jackson was used as a Union prison. It was here that the French Champagne magnate Charles Heidsieck was held for seven months on charges of spying.

The first fort on this location "San Felipe", was constructed in the 18th century during the Spanish control of Louisiana.

The fort served a role in protecting the United States from the British invasion in the War of 1812, seeing 9 days of battle in January 1815, the 9th to the 18th. Specifically, an action against British Navy vessels attempting to attack or bypass the fort.

The current fort was constructed along with Fort Jackson on the river's western bank as a coastal defense for New Orleans and the Mississippi, on urging of Andrew Jackson. The fort was the site of a twelve-day siege in April 1862 by the Union army during the American Civil War.

It was declared a National Historic Landmark in 1960.

In the 1930s the fort was used as a tanning factory. This explains the old railroad tracks and fire hydrants.

From 1978 through 1989 the fort complex served as the site of an intentional, nonsectarian spiritual community called Velaashby, named by conjoining the surnames the original and subsequent private property owners respectively. The community members numbered as many as 16 at any one time and were known as the Christos family. They lived in four buildings--three two-story officers quarters and an officers club--that remained from the re-fortification of the site during the 1898 Spanish-American War.

Fort St. Philip remains privately owned and in a state of bad deterioration. It was heavily damaged in hurricanes Katrina and Rita. According to the National Park Service, the owner reported that only the original brick fort and the concrete structures from the time of the Spanish-American War remain.

The site is accessible only by boat or helicopter, and following erosion of the small levee is now subject to flooding during high water levels of the Mississippi River.