Leon Janney's movie debut came with Victor Sjöström's The Wind starring Lillian Gish. He soon began appearing in a string of movies portraying the boyhood incarnations of such actors as Ricardo Cortez, Reginald Denny, and Conrad Nagel. Producer Hal Roach took notice of Janney and hired him to appear in the Our Gang comedy Bear Shooters as "Spud". However, Roach realized that he was too old to gel with the other members of the gang, and Bear Shooters marked his only appearance as a Little Rascal. In 1931 Janney starred in the second film adaptation of Booth Tarkington'sPenrod and Sam.
By the mid-1930s, Janney was considered the quintessential male juvenile star. As he entered his teenage years, he turned to radio and worked on the series The Parker Family, playing all-American boy Richard Parker. Though he preferred theater work, his radio work allowed him to become a master dialectician. After serving in World War II as a translator, he continued working in radio and theatre. Though blacklisted in the 1950s, Janney continued to work regularly due to his preference for theatrical work, appearing in such plays as The School for Scandal and The Gazebo.
By the 1960s, Janney appeared in bit roles on such television shows as Car 54, Where Are You?, The Defenders and The Jackie Gleason Show. He also made his first film appearance in more than a decade, playing a sympathetic guard in The Last Mile. Janney was also the spokesman for the New York Mets in their Rheingold Beer commercials for the team's first two seasons (1962-1963). In his final years, he was a regular the television shows Another World and The Edge of Night.
Janney died of cancer on October 28, 1980, in Guadalajara, Jalisco, Mexico.