The Missouri Compromise (March 3, 1820) was a United States federal legislation that stopped northern attempts to forever prohibit slavery's expansion by admitting Missouri as a slave state and Maine as a free state in exchange for legislation which prohibited slavery in the remaining Louisiana Purchase lands north of the 36°30′ parallel. The 16th United States Congress passed the legislation on March 3, 1820, and President James Monroe signed it on March 6, 1820.Earlier, in February 1819, Representative James Tallmadge Jr., a Democratic-Republican (Jeffersonian Republican) from New York, had submitted two amendments to Missouri's request for statehood that included restrictions on slavery. Southerners objected to any bill that imposed federal restrictions on slavery and believed that it was a state issue, as settled by the Constitution. However, with the Senate evenly split at the opening of the debates, both sections possessing 11 states, the admission of Missouri as a slave state would give the South an advantage. Northern critics including Federalists and Democratic-Republicans objected to the expansion of slavery into the Louisiana Purchase territory on the Constitutional inequalities of the three-fifths rule, which conferred Southern representation in the federal government derived from a state's slave population.

Jeffersonian Republicans in the North ardently maintained that a strict interpretation of the Constitution required that Congress act to limit the spread of slavery on egalitarian grounds. "[Northern] Republicans rooted their antislavery arguments, not on expediency, but in egalitarian morality." "The Constitution [said northern Jeffersonians], strictly interpreted, gave the sons of the founding generation the legal tools to hasten [the] removal [of slavery], including the refusal to admit additional slave states."When free-soil Maine offered its petition for statehood, the Senate quickly linked the Maine and Missouri bills, making Maine admission a condition for Missouri entering the Union as a slave state. Senator Jesse B. Thomas of Illinois added a compromise proviso that excluded slavery from all remaining lands of the Louisiana Purchase north of the 36° 30' parallel. The combined measures passed the Senate, only to be voted down in the House by Northern representatives who held out for a free Missouri. Speaker of the House Henry Clay of Kentucky, in a desperate bid to break the deadlock, divided the Senate bills. Clay and his pro-compromise allies succeeded in pressuring half of the anti-restrictionist House Southerners to submit to the passage of the Thomas proviso and maneuvered a number of restrictionist House northerners to acquiesce in supporting Missouri as a slave state. The Missouri question in the 15th Congress ended in stalemate on March 4, 1819, the House sustaining its northern antislavery position and the Senate blocking a slavery restricted statehood.

The Missouri Compromise was very controversial, and many worried that the country had become lawfully divided along sectional lines. The Kansas–Nebraska Act effectively repealed the bill in 1854, and the Supreme Court declared it unconstitutional in Dred Scott v. Sandford (1857), both of which increased tensions over slavery and contributed to the American Civil War. The compromise both delayed the Civil War and sowed its seeds; Thomas Jefferson writing contemporaneously predicted the line it had drawn would someday tear the Union apart. 40 years later, the North and South would split closely along the 36°30′ parallel and fight for four bloody years.