Jackson Barracks was established as a result of the Federal Fortifications Act, which was crafted in response to the War of 1812. Congress realized the lack of defense for coastal cities such as New Orleans.

First known as the "New Orleans Barracks," it was built in a quadrangle design, intended to be a rallying point for troops in the event of an attack. Buildings were constructed to serve as part of the fortification, with the backs having no outward facing windows. The structures were joined by a 10 foot brick outer wall that completed the fort.

Jackson Barracks first saw use during the Mexican-American War, which also caused the necessity of the nation's first Public Service Hospital for Veterans. The Barracks site cared for injured soldiers returning from Mexico.

The title "New Orleans Barracks" lasted from 1837 to July 7, 1866, when it was renamed "Jackson Barracks" to honor Battle of New Orleans hero General Andrew Jackson. General Sheridan was charged that same year with creating the first African-American cavalry regiment in peace time. Two of the four units that came to be known as the "Buffalo Soldiers" originated in New Orleans. One of these four divisions, the 25th Infantry Regiment, formed at Jackson Barracks in 1869. Their participation in the Indian wars and the Spanish-American War led to their being known as the "Buffalo Soldiers."

The federal government retained control until the end of WWI, when it gave the complex to the state of Louisiana. Originally an infantry post, its focus changed to a cavalry and artillery post. After WWI, when ownership transferred to the LA National Guard, it was made headquarters to the Washington Artillery and remains so. The Washington Artillery (technically the "141st Field Artillery Regiment") is the oldest continuous unit in the Louisiana National Guard and one of the oldest in the nation. It has been located in New Orleans since 1838.

During the Great Depression, state and federal funds (WPA, Works Progress Administration), put the Barracks through an extensive renovation project. During WWII, the federal government regained control, using the barracks as a port of embarkation. Following the war, control returned to the State, which uses it as the headquarters for the Louisiana National Guard.

In August 2005, the entire Jackson Barracks post was nearly destroyed by the flood waters of Hurricane Katrina. Breaches in the Industrial Canal Levee were largely responsible for submerging the site in as much as 20 feet of water. The majority of the post was re-built from scratch, at a total cost of $325 million. 17,500 square feet of buildings were constructed to original design, using original materials when possible.