Jefferson City traces its origins to the adjoining lots of several enslaved indigo, rice, and sugar cane plantations. The lands were independantly developed from the 1830s-1850s, resulting in several French fauburgs and Anglo neighborhoods including Delechaise, Bouligny, Rickerville, Hurtsville, Greenville, and several others.

While the areas were originally part of Orleans, the Louisiana State Legislature created Jefferson Parish in 1825, as a separate entity upriver from New Orleans. Riverfront properties, entertainment, and industry continued to expand with the introduction of the St. Charles and Carrollton railroads. Jefferson City was officially incorporated in 1850, and comprised the land between the cities of Lafayette and Carrollton all the way to the New Basin Canal.

Post Civil War Jefferson City was a tense and violent time, as residents were at odds with the Reconstructionist government. Tensions turned to violence with the state's deployment of the Metroplitan Police Force to overrule the local police authorites, as the city continued to resist Reconstruction efforts. Jefferson was initially resistant to being annexed by New Orleans, but in 1870 by an act of the state legislature, Jefferson City, along with Algiers across the river, were both subsumed by New Orleans. Jefferson City became the 6th Municipal District of New Orleans, comprised of wards 12, 13, and 14.