John O'Keefe or O'Keeffe may refer to:
Politics, government, and law John O'Keefe (Irish politician) (1827–1877), Member of Parliament for Dungarvan, 1874–1877 John O'Keefe (Australian politician) (1880–1942), Queensland state MP John Martin O'Keefe (born 1946), U.S. diplomat John J. O'Keefe, III (1975–2022), American police officer found dead outside a home in Canton, Massachusetts
Scientists John A. O'Keefe (astronomer) (1916–2000), American planetary scientist John O'Keefe (neuroscientist) (born 1939), American British neuroscientist, 2014 Nobel Prize laureate in Physiology or Medicine
Sportspeople John O'Keeffe (Cork hurler) (1894–1973), Irish hurler in the 1910s and 1920s John O'Keeffe (Gaelic footballer) (born 1951), Irish footballer who played for Kerry John O'Keeffe (Tipperary hurler) (born 1988), Irish hurler in the 2000s John O'Keeffe (Australian rules footballer) (born 1943), Australian rules footballer with Fitzroy John R. O'Keefe (born 1936), Australian rules footballer with Carlton Jack O'Keefe (1915–2000), Australian rules footballer
Other people John O'Keeffe (writer) (1747–1833), sometimes O'Keefe, Irish playwright John O'Keeffe (painter) ( 1797–1838), Irish painter John O'Keefe (playwright) (born 1940), American playwright Johnny O'Keefe (1935–1978), Australian rock and roll singer