James Monroe was born on April 28, 1758, in a wooded area of Westmoreland County, Virginia. The site is marked and is one mile from what is known today as Monroe Hall, Virginia. Monroe's father, Spence Monroe (1727–1774) was a moderately prosperous planter who also learned the carpentry trade. His mother, Elizabeth Jones Monroe (1730–1774), married Spence Monroe in 1752. They had five children live to maturity. His paternal 2nd great-grandfather immigrated to America from Scotland in the mid-17th century, Major Andrew Monroe (16-1688), who was descended from Robert Munro, 14th Baron of Foulis, chief of an ancient Scottish highland clan. In 1650 Andrew Monroe patented a large tract of land in Washington Parish, Westmoreland County, Virginia.

Between the ages of 11 and 16, Monroe studied at Campbelltown Academy, a school run by the Reverend Archibald Campbell of Washington Parish. There he excelled as a prodigious pupil and progressed through Latin and mathematics at a rate faster than that of most boys his age. John Marshall, later Chief Justice of the United States, was among his classmates. At the age of 16, Monroe enrolled in the College of William and Mary. However in 1774, the atmosphere on the Williamsburg campus was not conducive to study, and the prospect of rebellion against King George charged most of the students, including Monroe, with patriotic fervor. In June 1775, after the battles of Lexington and Concord, Monroe joined 24 older men in raiding the arsenal at the Governor's Palace. The 200 muskets and 300 swords they appropriated helped arm the Williamsburg militia. The following spring, Monroe dropped out of college and joined the Continental army. He never returned to earn a degree. Between 1780 and 1783, he studied law under Thomas Jefferson.

Monroe fought in the War of Independence, serving with distinction at the Battle of Trenton, where he was shot in his left shoulder. He spent three months in Bucks County, Pennsylvania, recuperating from his wound. He is depicted holding the flag in the famous painting of Washington Crossing the Delaware. Following his war service, he practiced law in Fredericksburg, Virginia.

James Monroe married Elizabeth Kortright (1768–1830), daughter of Laurence Kortright and Hannah Aspinwall Kortright, on February 16, 1786, in New York City. After a brief honeymoon on Long Island, the Monroes returned to New York to live with her father until Congress adjourned.

Monroe was elected to the Virginia House of Delegates in 1782 and served in the Continental Congress from 1783 to 1786. In Virginia the struggle in 1788 over the ratification of the proposed new Constitution involved far more than a simple clash between federalists and anti-federalists. Virginians held a full spectrum of opinions about the merits of the proposed change in national government. George Washington and James Madison were leading supporters; Patrick Henry and George Mason were leading opponents. The central actors in the ratification fight were those who held the middle ground in the ideological struggle. Led by Monroe and Edmund Pendleton, these "federalists who are for amendments," criticized the absence of a bill of rights and worried about surrendering taxation powers to the central government. Virginia ratified the Constitution in June 1788, largely because these men suspended their reservations and vowed to press for changes after the new government had been established. Virginia narrowly ratified the Constitution and Monroe ran for a House seat in the 1st Congress but was defeated by Madison. In 1790 he was elected United States Senator. He soon joined the "Republican" faction led by Jefferson and Madison and by 1791 was the party leader in the Senate.

Monroe resigned his Senate seat after being appointed Minister to France in 1794. As ambassador, Monroe was able to secure the release of Thomas Paine when the latter was arrested for his opposition to the execution of Louis XVI. He managed to free all the Americans held in French prisons, including Madame Lafayette. He issued American passports for the Lafayette family, (since they had been granted Citizenship), before she traveled to Lafayette's place of imprisonment, in Olmutz. A strong friend of the French Revolution, Monroe tried to assure France that Washington's policy of strict neutrality did not favor Britain. But American policy had come to favor Britain, and Monroe was stunned by the signing of the Jay Treaty in London. With France and Britain at war, the Jay Treaty alarmed and angered the French. Washington discharged Monroe from his office as Minister to France due to inefficiency, disruptive maneuvers, and failure to safeguard the interests of his country.

Monroe had long been concerned about untoward foreign influence on the presidency. He was alarmed at Spanish diplomat Don Diego de Gardoqui who in 1785 tried to convince Congress to allow Spain to close the Mississippi River to American traffic for 30 years. Here Monroe saw Spain overinfluencing the republic, which could have risked the loss of the Southwest or dominance of the Northeast. Monroe placed faith in a strong presidency and the system of checks and balances. In the 1790s he fretted over an aging George Washington being too heavily influenced by close advisers like Hamilton who was too close to Britain. Monroe favored France and so opposed the Jay Treaty in 1795. He was humiliated when Washington criticized him for his support of revolutionary France while he was minister to France. He saw foreign and Federalist elements in the genesis of the Quasi War of 1798–1800 and in efforts to keep Thomas Jefferson away from the presidency in 1801. As governor he considered using the Virginia militia to force the outcome in favor of Jefferson. Federalists responded in kind, some seeing Monroe as at best a French dupe and at worst a traitor. Monroe thus contributed to a paranoid style of politics.

Out of office, Monroe returned to practicing law in Virginia until elected governor there, serving from 1799 to 1802. He called out the state militia to suppress Gabriel's Rebellion. Gabriel and 26 other enslaved people who participated were hanged. In reaction, the Virginia and other legislatures passed restrictions on free blacks, as well as the education, movement and hiring out of the enslaved.

Under the first Jefferson administration, Monroe was dispatched to France to assist Robert R. Livingston to negotiate the Louisiana Purchase. Monroe was then appointed Minister to the Court of St. James (Britain) from 1803 to 1807. In 1806 he negotiated a treaty with Britain to replace the Jay Treaty of 1794, but Jefferson rejected it in 1807 as unsatisfactory, as the treaty contained no ban on the British practice of impressment of American sailors. As a result, the two nations moved closer toward the War of 1812. Old Republicans in the South, who claimed to adhere to the traditional party "principles of 1798", tried to coopt Monroe and have him elected president in the 1808 election. John Randolph of Roanoke took the lead in the movement to thwart President Jefferson's choice of James Madison as his successor. Jefferson had snubbed Monroe on foreign policy in 1807 and thereby alienated Monroe from the administration. Regular Republican control of key Virginia politicians, along with a number of other factors, however, insured Madison's 1808 electoral success.

Monroe returned to the Virginia House of Delegates and was elected to another term as governor of Virginia in 1811, but he resigned a few months into the term. He then served as Secretary of State from 1811 to 1814. When he was appointed to the post of Secretary of War in 1814, he stayed on as the Secretary of State ad interim. At the war's end in 1815, he was again commissioned as the permanent Secretary of State, and left his position as Secretary of War. Thus from October 1, 1814, to February 28, 1815, Monroe effectively held both cabinet posts. Monroe stayed on as Secretary of State until the end of the James Madison Presidency, and the following day Monroe began his term as the new President of the United States.

During the administrations of Jefferson and Madison the congressional nominating caucus experienced little opposition. However in 1816, this situation changed. Not only Federalists objected to the caucus system but so did an indeterminate number of anti-Virginia Republicans led by the New York delegation. Disorganization and failure to agree on William H. Crawford, Daniel Tompkins, Henry Clay, or another possible contender weakened opposition to Monroe. The boycott by Virginia delegates of the March 12 caucus removed opponents' chances and Monroe received the caucus nomination four days later. With the Federalist Party in disarray due to the unpopularity of their opposition to the War of 1812, he was easily elected. The Federalists did not even name a candidate, though Rufus King of New York did run in opposition to Monroe under the Federalist banner. King carried but three states (Connecticut, Delaware, and Massachusetts) and won only 34 of 217 electoral votes cast. 

The collapse of the Federalists left Monroe with no organized opposition at the end of his first term, and he ran for reelection unopposed, the only president other than Washington to do so. A single elector from New Hampshire cast a vote for John Quincy Adams, preventing a unanimous vote in the electoral college. He made balanced Cabinet choices, naming a southerner, John C. Calhoun, as Secretary of War, and a northerner, John Quincy Adams, as Secretary of State. Only Henry Clay's refusal to accept a position kept Monroe from adding an outstanding westerner. Most appointments went to deserving Democratic-Republicans, but he did not try to use them to build the party's base. Indeed, he allowed the lower posts to take on diverse political appointees, which reduced anxiety and led to the naming of this period in American history as the "Era of Good Feelings." To build national trust, he made two long national tours in 1817. Frequent stops allowed innumerable ceremonies of welcome and good will. All the while the Federalist Party continued to diminish. The party maintained its vitality and organizational integrity at the state and local level but dwindled at the federal level due to redistricting. The party's Congressional caucus stopped meeting, and there were no notable national conventions after Monroe's last term.

During his presidency, Congress demanded high subsidies for internal improvements, such as for the improvement of the Cumberland Road. Monroe vetoed the Cumberland Road Bill, which provided for yearly improvements to the road, because he believed it to be unconstitutional for the government to have such a large hand in what was essentially a civics bill deserving of attention on a state by state basis. This sort of defiance underlined Monroe's populist ideals and added credit to the local offices that he was so fond of visiting on his speech trails.

The era of "good feelings" endured until 1824, and carried over to John Quincy Adams who was elected President by the House of Representatives in what Andrew Jackson alleged to be a "corrupt bargain." Monroe's popularity, however, was undiminished even when following difficult nationalist policies as the country's commitment to nationalism was starting to show serious fractures. The Panic of 1819 caused a painful economic depression. The application for statehood by the Missouri Territory, in 1819, as a slave state failed. An amended bill for gradually eliminating slavery in Missouri precipitated two years of bitter debate in Congress. The Missouri Compromise bill resolved the struggle, pairing Missouri as a slave state with Maine, a free state, and barring slavery north of the latitude 36/30' N forever. The Missouri Compromise lasted until 1857, when it was declared unconstitutional by the U.S. Supreme Court as part of the Dred Scott decision.

After the Napoleonic wars (which ended in 1815), almost all of Latin America revolted against Spanish or Portuguese rule and declared independence. Americans welcomed this development as a validation of the the spirit of Republicanism. Adams suggested delay in formal recognition until Florida was secured in 1819. The whole problem of imperial invasion was intensified by a Russian claim to the Pacific coast down to the fifty-first parallel and simultaneous European pressure to have all of Latin America returned to its colonial status. In March 1822 Monroe informed Congress that permanent stable governments had been established in the United Provinces of La Plata (present-day Argentina), Chile, Peru, Colombia, and Mexico. Adams, under Monroe's careful supervision, wrote the instructions for the ministers (ambassadors) to these new countries. They declared that the policy of the United States was to uphold republican institutions and to seek treaties of commerce on a most-favored-nation basis. The United States would support inter-American congresses dedicated to the development of economic and political institutions fundamentally differing from those prevailing in Europe. The articulation of an "American system" distinct from that of Europe was a basic tenet of Monroe's policy toward Latin America. Monroe took pride as the United States was the first nation to extend recognition and to set an example to the rest of the world for its support of the "cause of liberty and humanity." In his message to Congress on December 2, 1823, Monroe formally announced what was later called the Monroe Doctrine. He proclaimed the Americas should be free from future European colonization and free from European interference in sovereign countries' affairs. It further stated the United States' intention to stay neutral in European wars and wars between European powers and their colonies, but to consider any new colonies or interference with independent countries in the Americas as hostile acts toward the United States.

Although it is Monroe's most famous contribution to history, the speech was written by Secretary of State John Quincy Adams, who designed the doctrine in cooperation with Britain. Monroe and Adams realized that American recognition would not protect the new countries against military intervention to restore Spain's power. In October 1823 Richard Rush, the American minister in London, advised that Foreign Secretary George Canning was proposing that the U.S. and Britain jointly declare their opposition to European intervention. Britain, with its powerful navy, also opposed re-conquest of Latin America and suggested that the United States join in proclaiming a "hands off" policy. Galvanized by the British initiative, Monroe consulted with American leaders and then he and Adams formulated a plan. Ex-Presidents Jefferson and Madison counseled Monroe to accept the offer, but Adams advised, "It would be more candid ... to avow our principles explicitly to Russia and France, than to come in as a cock-boat in the wake of the British man-of-war." Monroe accepted Adams' advice. Not only must Latin America be left alone, he warned, but also Russia must not encroach southward on the Pacific coast. "...the American continents," he stated, "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." In 1823 the Monroe Doctrine pertained more to the Russians in North America than to the former Spanish colonies in South America. The result was a system of American isolationism under the sponsorship of the British navy. The Monroe Doctrine held that the United States considered the Western Hemisphere as no longer a place for European colonization; that any future effort to gain further political control in the hemisphere or to violate the independence of existing states would be treated as an act of hostility; and finally that there existed two different and incompatible political systems in the world. Therefore the United States promised to refrain from intervention in European affairs and demanded Europe to abstain from interfering with American matters. In the event there were few serious European attempts at intervention.

The relations with Spain over the purchase of Florida proved to be more troublesome, especially after General Andrew Jackson invaded that territory on what he believed to be the president's authorization, which Monroe later denied giving. But largely through the skillful work of John Quincy Adams, a treaty was signed with Spain in 1819 by which Florida was ceded to the United States in return for the assumption of $5,000,000 in claims and the relinquishment of any claims to Texas. Monroe began to formally recognize the young sister republics (the former Spanish colonies) in 1822. He and Adams had wished to avoid trouble with Spain until it had ceded the Floridas to the U.S., which was done in 1821. Monroe sparked a constitutional controversy when, in 1817, he sent General Andrew Jackson to move against Spanish Florida in order to pursue hostile Seminole Indians and punish the Spanish for aiding them. News of Jackson's exploits ignited a congressional investigation of the 1st Seminole War. Dominated by Democratic-Republicans, the 15th Congress was generally expansionist and more likely to support the popular Jackson. Ulterior political agendas of many congressmen dismantled partisan and sectional coalitions, so that Jackson's opponents argued weakly and became easily discredited. After much debate, the House of Representatives voted down all resolutions that condemned Jackson in any way, thus implicitly endorsing Monroe's actions and leaving the issue surrounding the role of the executive with respect to war powers unanswered.

Monroe believed that the Indians must progress from the hunting stage to become an agricultural people, noting in 1817, "A hunter or savage state requires a greater extent of territory to sustain it than is compatible with progress and just claims of civilised life." His proposals to speed up the assimilation process were ignored by Congress.

When his presidency was over on March 4, 1825, James Monroe lived at Monroe Hill on the grounds of the University of Virginia. This university's modern campus was Monroe's family farm from 1788 to 1817, but he had sold it in the first year of his presidency to the new college. He served on the college's Board of Visitors under Jefferson and then under the second rector and another former President James Madison, until his death.

Monroe had racked up many debts during his years of public life. As a result, he was forced to sell off his Highland Plantation (now called Ash Lawn-Highland; it is owned by his alma mater, the College of William and Mary, which has opened it to the public). Throughout his life, he was not financially solvent, and his wife's poor health made matters worse. For these reasons, he and his wife lived in Oak Hill, Virginia, until Elizabeth's death on September 23, 1830. In August 1825, the Marquis de Lafayette and President John Quincy Adams, were guests of the Monroes there. Upon Elizabeth's death in 1830, Monroe moved to New York City to live with his daughter Maria Hester Monroe Gouverneur who had married Samuel L. Gouverneur in the first White House wedding. In April 1831, John Quincy Adams visited him there.

Monroe died there from heart failure and tuberculosis on July 4, 1831, becoming the third president to die on July 4. His death came 55 years after the U.S. Declaration of Independence was proclaimed and 5 years after the death of the Presidents John Adams and Thomas Jefferson. He was originally buried in New York at the Gouverneur family's vault in the New York City Marble Cemetery. Twenty-seven years later in 1858 the body was re-interred to the President's Circle at the Hollywood Cemetery in Richmond, Virginia. The James Monroe Tomb is a U.S. National Historic Landmark.