Charles O'Brien may refer to:

• Charles O'Brien, 5th Viscount Clare (1673–1706)
• Charles O'Brien, 6th Viscount Clare (1699–1761), Irish military officer in French service
• Charles O'Brien, 7th Viscount Clare (1757–1774)
• Charles O'Brien (colonial administrator) (1859–1935), British Governor of the Seychelles (1912–1918) and Barbados (1918–1925)
• Charles O'Brien (cricketer) (1921–1980), Australian cricketer
• Charles F. X. O'Brien (1879–1940), United States Representative from New Jersey
• Charles H. O'Brien (1920–2007), State Senator and judge from Tennessee, United States
• Charles M. O'Brien (1875–1952), Member of the Legislative Assembly of Alberta, Canada (1909–1913)
• Charles P. O'Brien (born 1939), American research scientist
• Charlie O'Brien (born 1960), retired American baseball player
• Charlie O'Brien (racing driver) (born 1955), Australian racing driver
• Charles O'Brien (unionist) (1933-2020), American labor union organizer

• Charles Bryan (disambiguation)