Henry William de Saussure (August 16, 1763 – March 26, 1839) was an American lawyer, state legislator and jurist from South Carolina who became a political leader as a member of the Federalist Party following the Revolutionary War.

After the Federalist Party faded in the early 1820s, he was a voice for Unionist moderation before a rising tide of States Rights supporters swept the stage of all others in South Carolina a generation later.

Although deep political differences would eventually separate them, John C. Calhoun studied law in the offices of Henry de Saussure and Timothy Ford, his partner and brother-in-law.

As a founder and early trustee of the University of South Carolina in Columbia, one of the original buildings located on the Horseshoe at the center of the campus, DeSaussure College, was named in his honor.

His father, Daniel, was deemed to be more of a prize and sent to the British prisons at St. Augustine, Florida along with other leaders of the American rebellion captured in South Carolina.

The family was reunited at Philadelphia after Henry's father was released as part of a prisoner exchange following the surrender of British forces at Yorktown.

In addition to his father, Henry William de Saussure had three uncles who served as officers of the Continental Line during the American Revolution.