Mississippi Territory
At the time of his move to Natchez, Claiborne's brother William C. C. Claiborne was serving as governor and superintendent of Indian affairs for the Mississippi Territory.
Elected in 1804 to serve in the 3rd General Assembly of the Mississippi Territory, Claiborne experienced a rapid rise in prominence. In July 1804 he announced in the Natchez newspaper that he and Edmund Wooldridge were becoming business partners. As of 1805, Ferdinand Claiborne had a dry goods store in the Natchez District in partnership with Edmond Wooldridge. They announced a dissolution of the partnership in October 1805, while Claiborne carried selling assorted foodstuffs and sundries including Madeira wine, coffee, soap, tamarinds, and spermacetti candles.
Appointed colonel of the Militia of Adams County, in 1806 Claiborne was ordered to march a unit in support of General James Wilkinson during the Sabine expedition. On November 30, 1806, he dueled Captain Benjamin Farar on the Vidalia sandbar; they shot at each other "with a brace of dueling pistols at ten paces. After two rounds were fired without damage to either party, the challenger declared that his honor was satisfied." The feud continued into 1807, in part because Farar "considered Claiborne an arrogant martinet". A dispute involving Farar, Claiborne, and Governor Williams and review of militia troops led to the revocations of Claiborne's commissions as militia colonel and magistrate. Claiborne's former business partner Wooldridge died at age 32 in June 1807 at the White Apple Village after a year's illness. In October 1807 local planter and politician Joseph Sessions wrote to James Madison requesting intervention in the matter of Claiborne's commission.
In January 1807 he advertised for sale "two women and five children, two of them of sufficient size to pick cotton...to be sold low and a credit given until 1st March next."
As of 1812 he was a director of the Bank of Mississippi, capitalized at $500,000, along with Stephen Minor, Samuel Postlethwaite, William Shields, Wm. Brooks, John Hankerson, Lyman Harding, Wm. G. Forman, Jeremiah Hunt, Lewis Evans, Jas. McIntosh, Thos. Wilkins, and Jas. C. Wilkins.