Thomas McKean developed a legal practice and political career spanning Delaware and Pennsylvania. Admitted to the Delaware bar in 1754, he held local administrative and judicial offices before entering the colonial assembly in 1762. At the Stamp Act Congress of 1765 he defended colonial rights, and he later helped organise resistance to British taxation. He represented Delaware in the Continental Congress from 1774 to 1783 alongside his state responsibilities.

An early advocate of independence, McKean supported the decisive congressional vote in July 1776 and became a signer of both the Declaration of Independence and the Articles of Confederation. He helped establish Delaware's government and briefly acted as the state's president in 1777. During 1781 he served briefly as president of the Continental Congress, an office preceding the federal presidency.

Appointed Pennsylvania's chief justice in 1777, he remained on the court until 1799. His work helped establish judicial authority amid Revolutionary upheaval. He supported ratification of the United States Constitution and participated in Pennsylvania's 1789–90 constitutional convention, favouring stronger executive and judicial institutions than those established by the state's first Revolutionary constitution.

Initially aligned with the Federalists, he moved toward Jefferson's Republicans and won Pennsylvania's governorship in 1799. His three terms were marked by partisan appointments, disputes with legislative radicals and resistance to attacks on judges. When Republican opponents backed Simon Snyder in 1805, McKean secured reelection with Federalist support, then removed some Republican adversaries from office. Bitter newspaper controversies and efforts to impeach him followed. Leaving the governorship in 1808, he remained interested in public affairs and supported preparations for Philadelphia's defence during the War of 1812. His career exposed tensions between popular politics and institutional independence.