Dickinson studied law in London at the Middle Temple and practiced law in Philadelphia (1757–60) before entering public life. He represented Pennsylvania in the Stamp Act Congress (1765) and drafted its declaration of rights and grievances. He won fame in 1767–68 as the author of the Letters from a Farmer in Pennsylvania, to the Inhabitants of the British Colonies, which appeared in many colonial newspapers. The letters helped turn opinion against the Townshend Acts (1767), under which new duties were collected to pay the salaries of royal officials in the Colonies. He also denounced the establishing of the American Board of Customs Commissioners at Boston to enforce the acts.

Dickinson was a delegate from Pennsylvania in the Continental Congress (1774–76) and was the principal author of the "Declaration . . . Setting Forth the Causes and Necessity of Their Taking Up Arms." He helped prepare the first draft of the Articles of Confederation (Confederation, Articles of) (1776–77) but voted against the Declaration of Independence (1776) because he still hoped for conciliation with the British. Although he was accused of being a loyalist, he later served in the patriot militia.

As a delegate from Delaware to the Federal Constitutional Convention (1787), Dickinson signed the U.S. Constitution (Constitution of the United States of America) and worked for its adoption. He later defended the document in a series of letters signed “Fabius.”

Dickinson College at Carlisle, Pennsylvania, chartered in 1783, was named in his honour.