The Big Knife marked the return of Odets to Broadway after a six-year hiatus in which he toiled in Hollywood as a screenwriter and motion picture director.

The play concerns the disillusionment of a movie star with the Hollywood's studio system and disgust with himself, as he has lost his idealism in the pursuit of success.

Castle signs the contract, but subsequently commits suicide with the knowledge that he can never reclaim his lost idealism that he had sacrificed for success.

The cast starred Frank H. Wilson (Russell), William Terry (Buddy Bliss), John Garfield (Charlie Castle), Leona Powers (Patty Benedict), Nancy Kelly (Marion Castle), Reinhold Schünzel (Nat Danzinger), J. Edward Bromberg (Marcus Hoff), Paul McGrath (Smiley Cox), Mary Patton (Connie Bliss), Theodore Newton (Hank Teagle), Joan McCracken (Dixie Evans), and John McKee (Dr. Frary).

New York Times theater critic Brooks Atkinson, in his review of the opening, admired the "distinguished art and craftsmanship" on display.