While she had a supporting role in "Thru Different Eyes" (1929), Sidney continued to work on stage and achieved a breakthrough in the title role of "Bad Girl" in 1930. Put under contract at Paramount, she was tapped to replace Clara Bow opposite Gary Cooper in "City Streets" and followed as the doomed factory worker in the film version of Theodore Dreiser's novel "An American Tragedy" (both 1931). Reportedly studio executive Budd Schulberg took an "interest" in the rising actress and loaned her to United Artists as an anguished young woman in "Street Scene" (also 1931). Typecast in these sweet-tempered roles as working-class heroines, Sidney nevertheless became a popular performer of the decade, working with some of the cinema's finest directors and actors. After playing the title role in "Madame Butterfly" (1935), she undertook a dual role paired with Cary Grant in the lightweight but engaging "Thirty Day Princess" (1934). Sidney offered a fine portrayal of a woman whose love for a gangster wreaks havoc in her life in "Mary Burns, Fugitive" (1935) and offered marvelous turns as the fiancee of Spencer Tracy in "Fury", Fritz Lang's study of mob rule, and as the unsuspecting wife of a turncoat in Alfred Hitchcock's "Sabotage" (both 1936). In the powerful "You Only Live Once" (1937), directed by Lang, she and Henry Fonda were powerful as a couple driven to a life of crime by a combination of bad luck and circumstance. A third pairing with the helmer, however, led to the imaginative misfire "You and Me" (1938).
By that time, Sidney's patented victimized waif was beginning to grow tiresome for both the actress and the audience. Now under contract to Walter Wanger, she had been promised the role of Cathy in "Wuthering Heights" but when the project was sold to Samuel Goldwyn was offered "Algiers" instead. Refusing to play yet another slum girl, Sidney decamped for the theater returning periodically to Hollywood in the 40s for roles in such efforts as "Blood on the Sun" (1945), opposite James Cagney, and the triangular romance "The Searching Wind" (1946), based on Lillian Hellman's play. As she aged, Sidney found good film roles difficult to find, although she was fine as Fantine in the 1952 remake of "Les Miserables". For much of the late 50s and all of the 60s, however, the actress concentrated on stage work, earning praise in such diverse parts as "Auntie Mame" and the wife in "The Fourposter". TV also provided opportunities; Sidney earned an Emmy nomination for a guest appearance on "The Defenders" in 1963.
After nearly twenty years, Sidney returned to features and picked up a Best Supporting Actress Oscar nomination as Joanne Woodward's overly critical mother in the character-driven "Summer Wishes, Winter Dreams" (1973). While her subsequent film appearances have been sporadic, she was memorable as a mental patient in "I Never Promised You a Rose Garden" (1977), the chain-smoking gatekeeper of purgatory in Tim Burton's "Beetlejuice" (1988) and Lukas Haas' grandmother in Burton's "Mars Attacks!" (1996). On the small screen, Sidney appeared alongside Helen Hayes, Mildred Natwick and Myrna Loy in the ABC thriller "Do Not Fold, Spindle or Mutilate" (1971) and played one of the airline hostages in the docudrama "Raid on Entebbe" (NBC, 1977). She was quietly affecting as a terminally-ill hospice resident in the Paul Newman-directed "The Shadow Box" (ABC, 1980) and as Robert Preston's senile wife in "Finnegan Begin Again" (HBO, 1985). Sidney earned a Golden Globe Award and an Emmy nomination as the understanding grandmother of an AIDS-stricken lawyer (Aidan Quinn) in the ground-breaking telefilm "An Early Frost" (NBC, 1985) before undertaking the regular role of one of several nursing home residents forced by fire to live in an orphanage in the treacly, short-lived drama "Morningstar/Eveningstar" (CBS, 1986). In 1998, she returned to regular series work on the remake of the ABC series "Fantasy Island".