John O'Keefe may refer to:
- John O'Keeffe (Irish writer) (1747–1833), sometimes O'Keefe, Irish playwright
- John O'Keeffe (Irish painter) (c.1797–1838), an Irish painter
- John A. O'Keefe (1916–2000), American planetary scientist
- John O'Keefe (cognitive neuroscientist)
- John O'Keefe (playwright), American playwright
- John O'Keeffe (footballer), Irish Gaelic footballer
- John Martin O'Keefe (born 1946), U.S. diplomat
- Johnny O'Keefe (1935–1978), Australian rock and roll singer
- John O'Keeffe (politician), Member of Parliament for Dungarvan, 1874–1877
- Jack O'Keefe, Australian rules footballer
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