Thomas O’Brien, Tom O’Brien, or Tommy O'Brien may refer to:

• Thomas C. O'Brien (1887–1951), American politician and lawyer
• Thomas J. O'Brien (Illinois politician) (1878–1964), Illinois politician
• Thomas J. O'Brien (Massachusetts politician) (contemporary), Massachusetts State Representative
• Thomas J. O'Brien (Michigan politician) (1842–1933), Michigan politician and U.S. ambassador
• Thomas P. O'Brien (born 1960), former United States Attorney for the Central District of California
• Sir Tom O'Brien (trade unionist) (1900–1970), British trade unionist and Member of Parliament

• Thomas O'Brien (footballer) (born 1991), Scottish footballer
• Tom O'Brien (American football) (born 1948), former American college football coach at NC State
• Tom O'Brien (footballer, born 1889) (1889–1963), Australian rules footballer for University
• Tom O'Brien (footballer, born 1904) (1904–1983), Australian rules footballer for Melbourne
• Tom O'Brien (jockey) (born 1986), Irish jockey
• Tom O'Brien (outfielder) (1873–1901), Major League Baseball outfielder/infielder
• Tom O'Brien (second baseman) (1860–1921), baseball player
• Tommy O'Brien (baseball) (1918–1978), Major League Baseball outfielder
• Tommy O'Brien (rugby union), Irish rugby union player
• Tommy O'Brien (basketball), American basketball player

• Thomas O'Brien (bishop) (1792–1874), Church of Ireland Bishop of Ossory, Ferns, and Leighlin
• Thomas O'Brien (interior designer) (born 1961), American designer
• Thomas D. O'Brien (1859–1935), co-founder of William Mitchell College of Law
• Thomas J. O'Brien (bishop) (1935-2018), Bishop of Phoenix, 1982–2003
• Thomas W. O'Brien (1859–1916), Canadian entrepreneur and pioneer
• Thomas Alexander O'Brien (1888–1948), New Zealand cinema owner and entrepreneur
• Tom O'Brien (actor, born 1890) (1890-1947), American film actor
• Tom O'Brien (actor) (born 1965), American film actor
• Tom O'Brien (swindler) (1851–1904), American confidence man and swindler