O'Brien spent a decade in plays on
Broadway and in the New York City area. O'Brien made his film debut in the
Vitaphone Varieties short film,
The Nightingale, produced in New York and released in August 1930. He was the lead in Paramount's
Personal Maid (1931), and appeared in a
Metro-Goldwyn-Mayer musical
Flying High (1931), supporting
Bert Lahr. He was
Irene Dunne's love interest in RKO's
Consolation Marriage (1932), then co-starred opposite a young
Bette Davis in ''
Hell's House'' (1932). O'Brien stayed in leads, going from studio to studio:
Scandal for Sale (1932), at Universal;
The Strange Case of Clara Deane (1932), at Paramount;
Hollywood Speaks (1932),
American Madness (1932) and
Virtue (1932). O'Brien played a heroic pilot in Universal's
Air Mail (1932), directed by
John Ford. While at that studio he was in the compelling
Laughter in Hell (1932) and
Destination Unknown (1933). At the small
Majestic Pictures he starred in
The World Gone Mad (1933).
Warner Bros O'Brien's first Warner Bros. movie was
Bureau of Missing Persons (1933), starring Bette Davis. He went to RKO for
Flaming Gold (1933) and MGM for
Bombshell (1933), then Warners signed O'Brien to a long-term contract. He would remain with the studio until 1940, when he left after a dispute over the terms of his contract renewal. O'Brien supported
Dick Powell in
College Coach (1933) and
Joan Blondell in ''
I've Got Your Number (1934). He was third lead to Barbara Stanwyck and Joel McCrea in Gambling Lady (1934), then was with Powell again in Twenty Million Sweethearts'' (1934).
Here Comes the Navy (1934) was O'Brien's first film with
James Cagney, also under contract to Warners. The two originally met in 1926 and remained friends for almost six decades. After O'Brien's death, Cagney referred to him as his "dearest friend." "That was a sweetheart," he said. "Jimmy's grand to work with," said O'Brien in 1935. "You couldn't ask for a better partner but there's a limit to all that. I think one picture a year with Jimmy would be fine. But as it is I've been with him in every uniform – the army, the navy, the police, the marines, the air corps – and it's always a case of me falling for his girl or him falling for mine. It gets tiresome... I don't just want to be a fast-talking Charlie all my life." Warners gave him some starring parts:
I Married a Doctor (1936), ''
Public Enemy's Wife (1936), China Clipper (1936), The Great O'Malley (1937), and Slim (1937) with Henry Fonda. He was Captain of the Guard (on special leave from the US Army) in San Quentin (1937) opposite Humphrey Bogart, romanced Blondell in Back in Circulation (1937) and was a veteran sailor in Submarine D-1'' (1938). O'Brien was pulled out of
Swing Your Lady to co-star with
Kay Francis in
Women Are Like That (1938) and was back with Powell for
Cowboy from Brooklyn (1938). He and Cagney reteamed for
Boy Meets Girl (1938), and he was meant to be back with Powell in
Garden of the Moon (1938), but Powell refused to do it – he was replaced by
John Payne. O'Brien had one of his best ever roles as the former street kid turned priest in
Angels with Dirty Faces (1938) with Cagney. He was with Blondell in
Off the Record (1939) and
The Kid from Kokomo (1939), and co-starred with
Gale Page in
Indianapolis Speedway (1939). He went over to Paramount for
The Night of Nights (1939), part of a deal in which Warners bought the rights to
The Old Maid from Paramount. He then made
Slightly Honorable (1939) for United Artists. Back at Warner Bros he was reunited with Cagney for
The Fighting 69th (1940) then made
Castle on the Hudson (1940) with Sheridan and
John Garfield. He was a cop in ''
'Til We Meet Again (1940), with Cagney and Sheridan in Torrid Zone (1940). He co-starred with Garfield and Frances Farmer in Flowing Gold'' (1940). O'Brien was then given his best known role, as the famous
University of Notre Dame football coach
Knute Rockne in
Knute Rockne, All American (1940). In the film, he gave the speech to "win just one for the Gipper," referring to recently deceased football player,
George Gipp, portrayed in the film by a young
Ronald Reagan. Reagan later used this saying as a slogan for his campaign for president in 1980. O'Brien was at a career peak. He was considered for the role of
Alvin York in the film
Sergeant York. From this high point, however, O'Brien left Warner Bros in July 1940.
Leaving Warner Bros in
Riffraff (1947) After he left Warner Bros. in 1940, O'Brien signed a contract with
20th Century Fox for two films a year. However they ended up not using him. He signed with
Columbia Pictures to make two films a year. He was in
Escape to Glory (1940), then was idle for a year before making
Two Yanks in Trinidad (1942) with
Brian Donlevy and
Flight Lieutenant (1942) with
Glenn Ford. At Universal he was in
Broadway (1942) with
George Raft.
RKO Soon he signed a contract with
RKO and appeared in several movies for that studio.) At RKO he did
Having Wonderful Crime (1946) and
Man Alive (1945). For Columbia he made
Perilous Holiday (1946). In 1946 he starred in the successful
film noir suspense film,
Crack-Up. He was in a thriller,
Riffraff (1947) and another biopic
Fighting Father Dunne (1948). He followed it with
The Boy with Green Hair (1948), and
A Dangerous Profession (1949) with Raft. While working as a Hollywood contract player, O'Brien made occasional appearances on the radio in the 1930s and 1940s. In 1946 he collaborated with the contralto
Kate Smith on the popular
Viva America program for the
CBS radio network. In the summer of 1947, he starred with
Lynn Bari in
Summer Theater, a program "dramatizing episodes in the life of a small town druggist." ==Later career==