Six of its companies formed the 5th Louisiana Infantry Battalion organized in September 1861, which fought in the Battle of Belmont as cannoneers.

After service at Island Number Ten, Fort Pillow, and the Siege of Corinth, the regiment was disbanded due to its high desertion rate.

Six companies from the Jackson Regiment were sent to Columbus, Kentucky in August, where they were organized as the 5th Louisiana Infantry Battalion by an order of General Leonidas Polk on 20 September.

[3] The battalion was expanded to the 21st Louisiana Infantry Regiment at Columbus on 9 February 1862 by the addition of four new companies, bringing it to 784 men.

The majority of the men of the regiment went to the 1st Louisiana Regulars, with 99 of these transfers documented in surviving records.