- Had been playing Walter Burns in "The Front Page" on Broadway before being tapped to appear in the 1931 film (The Front Page (1931)). The studio, confusing Burns with the other lead role, Hildy Johnson, offered O'Brien the latter role, assuming it was the one he had played onstage. He took the job, not informing them of their mistake.
- First met his lifelong friend Spencer Tracy when Tracy enrolled at Milwaukee's Marquette Academy in 1917.
- He and his wife had one biological child and three adopted children: Sean O'Brien, Terry O'Brien, Brigid O'Brien and Mavourneen O'Brien.
- Formed his own production company in 1944, which made only one film: Secret Command (1944).
- Met his wife Eloise while appearing at the Selwyn Theatre in Chicago in 1927.
- Interred at Holy Cross Cemetery in Culver City, CA.
- Appeared in three films that have been selected for the National Film Registry by the Library of Congress as being "culturally, historically or aesthetically" significant: The Front Page (1931), Knute Rockne All American (1940) and Some Like It Hot (1959).
- He wore a toupee.
- His final acting role was as a guest star in an episode of Happy Days (1974). The series was set in Milwaukee, WI, which was O'Brien's hometown.
- Was awarded two stars on the Hollywood Walk of Fame: for Motion Pictures at 1531 Vine St. and for Television at 6240 Hollywood Blvd.
- Attended Marquette Academy and Marquette University in Milwaukee, WI.
- Politically, he was extremely right-wing.
- Alumnus of the AADA (American Academy of Dramatic Arts), Class of 1922.
- Member and 1st Vice-President (beneeth President Gene Buck) of the Catholic Actors Guild of America (1945).
- Member of the Irish Mafia of Hollywood.
- Appeared in three Oscar Best Picture nominees: The Front Page (1931), Here Comes the Navy (1934) and Flirtation Walk (1934).
- Had appeared with Henry O'Neill in 11 films: Flirtation Walk (1934), Twenty Million Sweethearts (1934), I've Got Your Number (1934), Oil for the Lamps of China (1935), The Great O'Malley (1937), Submarine D-1 (1937), Knute Rockne All American (1940), Castle on the Hudson (1940), The Fighting 69th (1940), 'Til We Meet Again (1940) and The People Against O'Hara (1951).
- He was the celebrity spokesman for Blatz Beer.
- He was a major supporter of Francisco Franco in the Spanish Civil War.
- Biography in: "The Scribner Encyclopedia of American Lives". Volume One, 1981-1985, pages 607-608. New York: Charles Scribner's Sons, 1998.
- Mentioned in Rise and Shine (1941).
- At the time of his death, he lived at 12953 Marlboro St., at the corner of lower Rockingham, in Brentwood. He lived across the street from Dr. John "Jack" Davis Jack Davis. O'Brien's home was purchased by Tom Laughlin and Dolores Taylor.
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