In 1921, Schildkraut played the title role in the first American stage production of Ferenc Molnár’s Liliom, the play that would eventually become the basis for Rodgers and Hammerstein’s Carousel. He then began working in silent movies, although he did return to the stage occasionally. He had early success in film as the Chevalier de Vaudrey in D. W. Griffith’s Orphans of the Storm with Lillian Gish. Later, he was featured in Cecil B. DeMille’s epic 1927 film The King of Kings, as Judas Iscariot. Schildraut’s father Rudolf also appeared in the film. Joseph Schildkraut also played a Viennese-accented, non-singing Gaylord Ravenal in the 1929 part-talkie film version of Edna Ferber’s Show Boat. The character as written in the 1929 film was much closer to Ferber’s original than to the depiction of him in the classic Kern and Hammerstein musical play based on the novel as well as the 1936 and 1951 film versions of the musical, but the 1929 film was not a critical or box-office success.

Schildkraut was married three times. His first marriage was to actress Elise Bartlett in 1923; they divorced in 1931. He married Mary McKay in 1932, until her death on February 17, 1962. In 1963, Schildkraut married Leonora Rogers, who survived him. Schildkraut died at his home in New York City of a heart attack. His father had died at the same age, also of a heart attack.

Schildkraut is perhaps best remembered today for playing the role of Otto Frank in both the original stage production and film version of The Diary of Anne Frank (1959). He was also an active character actor and appeared in guest roles on several early television shows, including the Hallmark Hall of Fame, in which he played Claudius in the 1953 television production of Hamlet, with Maurice Evans in the title role. Schildkraut also hosted and starred in Joseph Schildkraut Presents, a short-lived series on the DuMont Television Network from October 1953 to January 1954.

In 1961, during the third season of The Twilight Zone, he made his first appearance on episode 9, “Deaths-Head Revisited”. He later played an elderly man in “The Trade-Ins” in season 3, episode 31 of the same show. In 1963, he was nominated for a Best Actor Emmy Award for his performance in a guest starring role on NBC’s Sam Benedict legal drama which starred Edmond O’Brien and Richard Rust.