Jefferson was primarily of English ancestry, born and educated in colonial Virginia. He graduated from the College of William & Maryand briefly practiced law, at times defending slaves seeking their freedom. During the American Revolution, he represented Virginia in the Continental Congress that adopted the Declaration, drafted the law for religious freedom as a Virginia legislator, and he served as a wartime governor (1779–1781). He became the United States Minister to France in May 1785, and subsequently the nation's first Secretary of State in 1790–1793 under President George Washington. Jefferson and James Madison organized the Democratic-Republican Party to oppose the Federalist Party during the formation of the First Party System. With Madison, he anonymously wrote the controversial Kentucky and Virginia Resolutions in 1798–1799, which sought to embolden states' rights in opposition to the national government by nullifying the Alien and Sedition Acts.

As President, Jefferson pursued the nation's shipping and trade interests against Barbary pirates and aggressive British trade policies. He also organized the Louisiana Purchase, almost doubling the country's territory. As a result of peace negotiations with France, his administration reduced military forces. He was reelected in 1804. Jefferson's second term was beset with difficulties at home, including the trial of former Vice President Aaron Burr. American foreign trade was diminished when Jefferson implemented the Embargo Act of 1807, responding to British threats to U.S. shipping. In 1803, Jefferson began a controversial process of Indian tribe removal to the newly organized Louisiana Territory, and he signed the Act Prohibiting Importation of Slaves in 1807.

Jefferson mastered many disciplines, which ranged from surveying and mathematics to horticulture and mechanics. He was a proven architect in the classical tradition. Jefferson's keen interest in religion and philosophy earned him the presidency of the American Philosophical Society. He shunned organized religion but was influenced by both Christianity and deism. He was well versed in linguistics and spoke several languages. He founded the University of Virginia after retiring from public office. He was a prolific letter writer and corresponded with many prominent and important people throughout his adult life. His only full-length book is Notes on the State of Virginia (1785), considered the most important American book published before 1800.

Although regarded as a leading spokesman for democracy and republicanism in the era of the Enlightenment, Jefferson's historical legacy is mixed. He owned and profited from several plantations which were worked by slaves throughout all of his adult life. There is evidence that after his wife Martha died in 1782, Jefferson fathered children with Martha’s half-sister Sally Hemings, who was his slave. Some modern scholarship has been critical of Jefferson's private life, pointing out the contradiction between his ownership of slaves and his famous declaration that "all men are created equal." He continues to rank highly among U.S. presidents. Presidential scholars and historians generally praise Jefferson's public achievements, including his primary authorship of the Declaration of Independence, advocacy of religious freedom and tolerance in Virginia, and his oversight of the Louisiana Purchase.