Charles Cotesworth Pinckney combined military service, constitutional politics, and diplomacy with the interests of South Carolina's slaveholding elite. After returning from legal training in England, he practiced law and entered colonial public life. During the Revolution he commanded South Carolina troops, served with Washington's army in the Philadelphia campaign, and fought in the southern theater. Captured after Charleston's fall in 1780, he remained a prisoner until his exchange in 1782.

At the Constitutional Convention of 1787, Pinckney supported a stronger national government while defending the economic and political demands of southern planters. He argued against an immediate prohibition of the Atlantic slave trade and helped secure the compromise postponing federal prohibition until 1808. His work for national union therefore accompanied an explicit defense of slavery. He signed the Constitution and became a leading advocate of ratification in South Carolina.

Washington appointed him minister to France in 1796, but the French government refused to receive him amid disputes over American neutrality and relations with Britain. John Adams then named him to a three-man negotiating commission with John Marshall and Elbridge Gerry. Demands for payments before substantive negotiations produced the XYZ Affair and helped bring about the undeclared naval conflict with France. Pinckney returned home and briefly held a senior army command during the crisis.

A Federalist, he was the party's vice-presidential candidate in 1800 and its presidential nominee in 1804 and 1808, losing the latter contests to Thomas Jefferson and James Madison. He subsequently devoted attention to plantation management, agriculture, education, and civic organizations in South Carolina. His plantations depended on enslaved labor. He is distinct from his younger cousin Charles Pinckney, who also represented South Carolina at the Constitutional Convention and had a separate political career.