John Spence may refer to:
- John S. Spence (1788–1880), American Senator from Maryland
- John Spence (politician) (1920–1986), British Conservative MP 1970–1986
- John Spence (musician) (1969–1987), founding member of the band No Doubt
- John Spence (HMRC), HMRC Non-executive Director
- John Spence (author), Named on of the top 100 Business Thought Leaders in America in 2011