The revelation in 1801 of the secret agreement of 1800, whereby Spain retroceded Louisiana to France, aroused uneasiness in the United States both because Napoleonic France was an aggressive power and because Western settlers depended on the Mississippi River for commerce. In a letter to the American minister to France, Robert R. Livingston (1746–1813; see Livingston, family), President Jefferson stated that The day that France takes possession of New Orleans … we must marry ourselves to the British fleet and nation. Late in 1802 the right of deposit at New Orleans, granted to Americans by the Pinckney treaty of 1795, was withdrawn by the Spanish intendant (Louisiana was still under Spanish control). Although Spain soon restored the right of deposit, the acquisition of New Orleans became of paramount national interest.

Jefferson instructed Livingston to attempt to purchase the Isle of Orleans (i.e., New Orleans) and West Florida from France. He appointed James Monroe minister extraordinary and plenipotentiary to serve with Livingston. Congress granted the envoys $2 million to secure their object.

The international situation favored the American diplomats. Louisiana was of diminishing importance to France. The costly revolt in Haiti forced the French emperor Napoleon I to reconsider his plan to make Hispaniola the keystone of his colonial empire, and impending war with Great Britain made him question the feasibility of holding Louisiana against that great naval power. He decided to sell Louisiana to the United States.

On Apr. 11, 1803, the French foreign minister Charles Maurice de Talleyrand opened negotiations by asking the surprised Livingston what the United States would give for all of Louisiana. Bargaining began in earnest the next day, on Monroe's arrival in Paris. On Apr. 29, the U.S. envoys agreed to pay a total of $15 million to France; about $3,750,000 of this sum covered claims of U.S. citizens against France, which the U.S. government agreed to discharge. The treaty, dated Apr. 30, 1803, was signed several days later. Jefferson's scruples about the constitutionality of the purchase were overcome by his fears that Napoleon might change his mind (as intimated in reports from Livingston) and by the overwhelming public approval of the Louisiana Purchase (although there was some objection from Federalists, especially in New England).

The treaty was ratified by the U.S. Senate in October, and the U.S. flag was raised over New Orleans on Dec. 20. The Louisiana Purchase, extending from the Mississippi River to the Rocky Mts. and from the Gulf of Mexico to British North America, doubled the national domain, increasing it c.828,000 sq mi (c.2,144,500 sq km). The final boundaries of the territory were not settled for many years (see West Florida Controversy), since the 1803 treaty did not set the limits of the region.