Isaac Donnom Witherspoon (December 3, 1803 - July 30, 1858) was a politician in South Carolina.
[1] He served in the state house and then the state senate.
He succeeded William K. Clowney as lieutenant governor and served from December 1842 until December 1844.
[2] He was succeeded by J. F. Ervin.
Isaac Witherspoon died of a stroke in 1858, aged 54.