Henry was a delegate to the First and Second Continental Congresses, where he signed the Petition to the King, which he assisted in drafting, and the Continental Association, although he was otherwise unimportant. Following the Gunpowder Incident, he won even more favor among the people of Virginia, both by his oratory before the convention and by advancing soldiers towards the colonial capital of Williamsburg until the royal government's stolen weapons were paid for. When the Fifth Virginia Convention backed independence in 1776, Henry sat on the committee that drafted the Virginia Declaration of Rights and the first Virginia Constitution. Henry was immediately chosen governor under the new legislation and completed 5 one-year periods.

Following his resignation as governor in 1779, Henry remained in the Virginia House of Delegates until 1784, when he began his final 2 tenuresas governor. Henry feared a powerful federal government after the national government's activities under the Articles of Confederation, thus he rejected to be a member of the 1787 Constitutional Convention. He vigorously opposed the United States Constitution's approval, both out of fear of strong local authority and because there was no Bill of Rights at the time. In his later years, he reverted to the profession of law, refusing multiple federal government positions. He had been a slaveholder his whole adult life and wished to see the society collapse, but he had no strategy other than to stop importing slaves. Henry is known for his oratory and for being a passionate supporter of the cause for independence.