For a time he attended Eton and other English schools.
In December 1786 he came to New Orleans, where he was associated with an uncle of the same name as merchant and landholder. The two owned properties in the neighboring districts of Baton Rouge and Natchez, and formed commercial connections with the upper Ohio and with Philadelphia. The younger Clark also served as clerk in the local office of the Spanish governor and was looked upon as an enterprising man of wealth, who was socially and politically ambitious but thoroughly honest and public-spirited. In 1798, when the Natchez district was transferred to the United States and organized as the Territory of Mississippi, both men renewed with Gen. Wilkinson, who accompanied the American troops thither, a business and social connection that had been established some ten years before. The younger Clark then became an American citizen. For a few months the Spanish governor permitted him to act in New Orleans as temporary American consul. In that capacity he submitted a partial report on the early commerce between Kentucky and New Orleans. He served as intermediary between the governor and Wilkinson and Andrew Ellicott, the American boundary commissioner, and helped to bring the trading activities of Philip Nolan to the attention of Jefferson. On July 16, 1801, Jefferson appointed Clark regular consul at New Orleans. Some months later, after a visit to the seat of government, where he dropped some hints of Wilkinson's earlier intrigues with the Spaniards, he made a hurried trip to France, and held interviews with the officials who were about to take possession of Louisiana. After his return, early in 1803, he continued his efforts to establish American control in New Orleans. He concerted measures with friends in that city to thwart the French Commissioner, Laussat, and tried to prevail upon Wilkinson and Gov. Claiborne to embody the regulars and the militia of Mississippi Territory and occupy New Orleans before the French arrived in force. Later, during the brief interregnum of the French Commissioner, he organized in connection with that official a local force to guard the city. He made two trading voyages to Vera Cruz in 1805-06 that were popularly supposed to have some connection with the Burr Conspiracy. When Burr first visited New Orleans in 1805, he bore a letter of introduction from Wilkinson to Clark, and the latter soon warned Wilkinson of the wild rumors that were beginning to cluster around Burr's movements. In the following year Claiborne at first charged Clark with complicity in the conspiracy but later retracted the charge. At that time, as earlier, he was a bitter opponent of Claiborne, and their animosity finally brought about a duel in the summer of 1807, in which the Governor was seriously wounded. In 1806 Clark was elected as delegate to Congress from Orleans Territory. While serving in that capacity he openly broke with Wilkinson and later secured for the committee of Congress that investigated the General's conduct much of its material. This service provoked a bitter attack on him and in reply he published his book, Proofs of the Corruption of Gen. James Wilkinson (1809), which furnishes much evidence of the General's treachery. Clark served only one term in Congress and withdrew from mercantile activities during the closing years of his life.
Between 1801 and 1806 he had formed with Madame Zulime Des Granges an irregular connection, of which two daughters were born and which gave rise some twenty years after his death to a half-century of litigation over his estate.