Richard Henry Lee moved from Virginia's planter legislature into a leading role in campaigning for American independence. A member of the House of Burgesses from 1758, he opposed parliamentary taxation and helped organize resistance through petitions, nonimportation, and committees of correspondence. He linked Virginia's local networks with opponents of British policy elsewhere. Like many members of his family and social class, he owned a plantation worked by enslaved people.

Virginia sent Lee to the Continental Congress in 1774. On June 7, 1776, acting on instructions from the Virginia convention, he introduced resolutions calling for independence, foreign alliances, and a confederation. Congress adopted the independence resolution on July 2, before approving the Declaration's explanatory text on July 4. Lee was the mover of the resolution rather than the principal author of the Declaration, which he later signed. His return to Virginia meant he did not serve on the drafting committee.

He continued congressional and state service through the Revolution, working on military, diplomatic, and governmental questions. Under the Articles of Confederation he returned to Congress and served as its president in 1784–1785. This was a presiding office within the confederation, distinct from the executive presidency established by the later Constitution. The period involved disputes over national finances, western lands, and the authority of Congress.

Lee distrusted the concentration of power in the Constitution proposed in 1787 and sought stronger safeguards for individual liberty and the states. After ratification he served as one of Virginia's first United States senators, from 1789 until his resignation in 1792. He supported amendments that became the Bill of Rights and served as president pro tempore of the Senate. His career thus connected the drive for separation from Britain with continuing debate over how much authority the national government should possess.