Sampson Williams was born in South Carolina on December 2, 1762, to Daniel and Ann (Echols) Williams. The family migrated to Tennessee in 1786 and settled in the Mero District (now Davidson County). Williams began operating a ferry on the Cumberland River at the meeting of the Eastern and Mero Districts in 1791. Governor Blount authorized him to raise men to defend the crossing the next year. Blount obtained permission to establish a larger outpost in 1794, and both Williams and his brother Oliver served as captains of the militia at the resulting Fort Blount. Although the Fort was turned over to Federal troops when Tennessee joined the Union in 1796, Williams continued living there for some time. Williams was also involved in several campaigns against the Creek Indians in Middle Tennessee. He commanded Andrew Jackson during one of these expeditions, and the two became lifelong friends.

Williams and his family later moved to Jackson County, Tennessee. In 1806, the County's seat was named Williamsburg in his honor. When the county seat moved to Gainesboro in 1817, Williams and his wife, Margarett Young (1780-1852), bought the courthouse and used it as a private residence. Williams died on February 1, 1841, in Williamsburg and is buried in Jackson County.