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- Eli M. Saulsbury (1817–1893), General Assembly and U.S. Senator from Delaware
- Gove Saulsbury (1815–1881), General Assembly and Governor of Delaware.
- Willard Saulsbury, Sr. (1820–1892), Chancellor of Delaware and U.S. Senator from Delaware
- Willard Saulsbury, Jr. (1861–1927), lawyer and U.S. Senator from Delaware
- Mary Ann Shadd (1823–1893), educator, newspaper publisher, abolitionist and suffragist; born in Wilmington
- Dave Sheridan (born 1969), actor
- Chris Short, Major League Baseball player
- Andrew Shue (born 1967), actor; born in Wilmington
- Elisabeth Shue (born 1963), actress; born in Wilmington
- Melanie Sloan, Executive Director of Citizens for Responsibility and Ethics in Washington
- Devin Smith, professional basketball player for Maccabi Tel Aviv
- Nathaniel B. Smithers (1818–1896), lawyer and U. S. Representative from Delaware
- Thomas Alfred Smyth, last Union General killed in the Civil War
- Ian Snell (born 1981), Major League Baseball player.
- Presley Spruance (1785–1863), General Assembly and U.S. Senator from Delaware
- W. Laird Stabler, Jr. (1930–2008), lawyer and Attorney General of Delaware
- J. George Stewart (1890–1970), architect and U.S. Representative from Delaware
- Michael Stewart (born 1977), professional boxer
- Charles C. Stockley (1819–1901), General Assembly and Governor of Delaware
- Thomas Stockton (1781–1846), soldier and Governor of Delaware
- Jacob Stout (1764–1857), General Assembly and Governor of Delaware.
- Susan Stroman (born 1954), choreographer, director; born in Wilmington
- James Sykes (1725–1792), General Assembly and Continental Congress
- James Sykes (1761–1822), General Assembly and Governor of Delaware.
Read more about this topic: List Of People From Delaware