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Witherspoon may refer to:
- John Witherspoon College, a non-denominational Christian liberal arts college in Rapid City, South Dakota
- Witherspoon Cottage, a historic cure cottage located at Saranac Lake, New York
- Witherspoon Building, a historic office building located in Philadelphia, Pennsylvania.
- Witherspoon-Hunter House, a historic home located at York, York County, South Carolina
- Witherspoon Institute, a think tank in Princeton, New Jersey
- John Witherspoon Middle School in Princeton, New Jersey
- The Witherspoon Lodge of Free and Accepted Masons, No. 111, historic building in Mount Dora, Florida
- Witherspoon v. Illinois, 391 U.S. 510 (1968), U.S. Supreme Court case regarding selection of jurors in capital cases
- Witherspoon questions, questions asked of prospective jurors in capital cases in the United States about their views regarding capital punishment
- Witherspoon Street School for Colored Children, a former school in Princeton, New Jersey
- The Curious Case of Edgar Witherspoon, the first episode of the third season (1988–89) of the television series The Twilight Zone
- Miss Witherspoon, a play written in 2005 by Christopher Durang
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