As a member of the First Continental Congress, where he signed the Continental Association, Dickinson drafted most of the 1774 Petition to the King, and then, as a member of the Second Continental Congress, he wrote the 1775 Olive Branch Petition. Both of these attempts to negotiate with King George III of Great Britain failed. Dickinson also reworked Thomas Jefferson's language to write the final draft of the 1775 Declaration of the Causes and Necessity of Taking Up Arms.

While in Congress, Dickinson served on the committee that wrote the Model Treaty, a template for seeking alliances with foreign countries, but he opposed independence from Great Britain. He either abstained or was absent from the vote on the Declaration of Independence and refused to sign the document after its passage. Nevertheless, Dickinson wrote the first draft of the 1776–1777 Articles of Confederation and Perpetual Union and served as a militia officer during the Revolution. He later was elected president of the 1786 Annapolis Convention, which called for the Constitutional Convention of 1787, and as a delegate from Delaware, he signed the United States Constitution.

One of the wealthiest men in the British American colonies, Dickinson served as president of Delaware (1781–1783) and president of Pennsylvania (1782–1785).