After studying law and becoming a protégé of Virginia Governor Thomas Jefferson, Monroe was admitted to the Virginia bar and practiced in Fredericksburg, Virginia.

In 1800, Monroe called out the state militia to suppress Gabriel's Rebellion, a slave rebellion originating on a plantation six miles from the capital of Richmond. Gabriel Prosser, a literate enslaved blacksmith, and 27 other enslaved people who participated were all hanged for treason.

Rufus King was the de facto Federalist nominee for president in 1816, losing in a landslide to Monroe. The Federalist Party became defunct at the national level after this election, and King was the last presidential nominee the party fielded.

As Monroe's wife, Elizabeth Jane Monroe was the First Lady of the United States from 1817 to 1825. Due to the fragile condition of Elizabeth's health, however, many of the duties of official White House hostess were assumed by her eldest daughter, Eliza Monroe Hay.

The Panic of 1819 was the first widespread and durable financial crisis in the United States and some historians have called it the first Great Depression. It was followed by a general collapse of the American economy that persisted through 1821. The Panic heralded the transition of the nation from its colonial commercial status with Europe toward an independent economy.

When accusations were published against Alexander Hamilton based on personal letters he had shown Monroe as proof of his innocence in the Reynolds Affair, he believed Monroe had leaked the information and challenged him to a duel. Monroe replied "I am ready, get your pistols." Monroe chose Aaron Burr as his second. Burr worked as a negotiator between the two parties, believing they were both being "childish," and eventually helped settle matters. Ironically, Burr himself would later kill Hamilton in an unrelated duel.

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, William Plumer, cast a vote for John Quincy Adams, preventing a unanimous vote in the Electoral College.

Monroe was the last U.S. president to wear a powdered wig tied in a queue, a tricorne hat and knee-breeches according to the style of the late 18th century, earning him the nickname "The Last Cocked Hat". He is also the last president to have never been photographed.