Jack O'Brien may refer to:

• Jack O'Brien (American football) (born 1932), American football player
• Jack O'Brien (catcher) (1860–1910), Major League Baseball player
• Jack O'Brien (cricketer) (1886–1939), New Zealand cricketer
• Jack O'Brien (footballer, born 1887) (1887–1959), Australian rules footballer for Essendon and Fitzroy
• Jack O'Brien (footballer, born 1893) (1893–1934), Australian rules footballer for South Melbourne
• Jack O'Brien (footballer, born 1898) (1898–1966), Australian rules footballer for Essendon and Footscray
• Jack O'Brien (footballer, born 1906) (1906–1970), Australian rules footballer for South Melbourne and Hawthorn
• Jack O'Brien (outfielder) (1873–1933), American baseball player
• Jack O'Brien (wrestler) (1910–1982), American-born Mexican professional wrestler
• Philadelphia Jack O'Brien (1878–1942), American boxer, former light heavyweight boxing champion of the world
• Young Jack O'Brien (1894–?), lightweight boxer from Pennsylvania

• Jack O'Brien (director) (born 1939), American theatre director and producer
• Jack O'Brien (jazz pianist) (1903–1982), big band pianist and songwriter
• John B. O'Brien (known as Jack, 1884-1936), American actor and film director
• Jack O'Brien (editor) (born 1980), American editor
• Jack O'Brien (Artist) (born 1993), British Artist

• John O'Brien (disambiguation)
• Jack O'Brian (1914–2000), journalist