Janney was born in Dayton, Ohio, the daughter of Macy Brooks (née Putnam), a former actress and homemaker, and Jervis Spencer Janney, Jr., a real estate developer and jazz musician. She has an older brother, Jay, and a younger brother, Hal. She attended The Miami Valley School in Dayton, where she was named a distinguished alumna in 2004, and the Hotchkiss School in Connecticut. She then attended Kenyon College. At Kenyon, Janney studied under another Kenyon alum, Paul Newman. She went on to study drama at the Neighborhood Playhouse in New York and the Royal Academy of Dramatic Art in London. She attended The Neighborhood Playhouse the same years as actor Dylan McDermott.