New foreign policy challenges arose even as Congress struggled with the slavery issue. In 1816, U.S. troops led by General Andrew Jackson invaded Spanish Florida in search of Seminole Indians harboring escaped slaves. Once there, Jackson declared himself the commander of northern Florida, demonstrating his power in 1818 by executing two British men who he claimed were dangerous enemies. In asserting rule over the territory, and surely in executing the two British subjects on Spanish land, Jackson had gone too far. Privately, President Monroe was distressed and pondered court-martialing Jackson, prevented only by Jackson’s immense popularity as the hero of the battle of New Orleans. Instead, John Quincy Adams, the secretary of state, negotiated with Spain the Adams-Onís Treaty, which delivered Florida to the United States in 1819 and finally settled the disputed borders of the Louisiana Purchase. In exchange, the Americans agreed to abandon any claim to Texas or Cuba. Southerners viewed this as a large concession, having eyed both places as potential acquisitions for future slave states.

Spain at that moment was preoccupied with its colonies in South America. One after another, Chile, Colombia, Peru, and finally Mexico declared themselves independent in the early 1820s. To discourage Spain and other European countries from reconquering these colonies, Monroe in 1823 formulated a declaration of principles on South America, known in later years as the Monroe Doctrine. The president warned that “the American Continents, by the free and independent condition which they have assumed and maintain, are henceforth not to be considered as subjects for future colonization by any European power.” Any attempt to interfere in the Western Hemisphere would be regarded as “the manifestation of an unfriendly disposition towards the United States.” In exchange for noninterference by Europeans, Monroe pledged that the United States would stay out of European struggles.