George Read established a successful legal practice in New Castle before becoming one of Delaware's principal revolutionary and constitutional leaders. As crown attorney general for the Three Lower Counties from 1763 to 1774, he challenged parliamentary taxation while still holding royal office. He entered the colonial assembly and represented Delaware in the Continental Congress from 1774.

Read initially favored reconciliation and voted against the resolution for independence in July 1776. Once Congress adopted separation, however, he accepted the decision and signed the Declaration. He helped frame Delaware's constitution and served in its legislative council. When British forces captured state president John McKinly in 1777, Read assumed executive responsibilities during the emergency, holding the presidency until Caesar Rodney took office in 1778.

His later public work included service in state government and the Confederation's court for maritime captures. He attended the Annapolis Convention in 1786 and the Constitutional Convention in 1787. At Philadelphia he supported a strong national government while insisting that small states retain effective protection against their larger neighbors. He advocated equal state representation in the Senate and signed the final Constitution. He also signed for John Dickinson at Dickinson's request after the latter left the convention because of illness.

Read promoted ratification in Delaware, which became the first state to approve the Constitution in December 1787. Elected to the new United States Senate, he served from 1789 to 1793 and supported the Federalist financial program, including the national bank and assumption of state debts. He resigned to become Delaware's chief justice and remained in that office until his death in 1798. His initial caution did not prevent service to the new political order. His work joined state leadership and legal administration with national authority and safeguards for small states.