Taking its name from a popular series of mystery novels, Inner Sanctum Mysteries debuted over NBC's Blue Network in January 1941. It featured one of the most memorable and atmospheric openings in radio history: an organist hit a dissonant chord, a doorknob turned, and the famous "creaking door" slowly began to open. Every week, Inner Sanctum Mysteries told stories of ghosts, murderers, and lunatics. Produced in New York, the cast usually consisted of veteran radio actors, with occasional guest appearances by such Hollywood stars Boris Karloff, Peter Lorre, and Claude Rains. What made Inner Sanctum Mysteries unique among radio horror shows was its host, a slightly sinister sounding fellow originally known as "Raymond." The host had a droll sense of humor and an appetite for ghoulish puns, and his influence can be seen among horror hosts everywhere, from the Crypt-Keeper to Elvira. Raymond Edward Johnson was the show's host until 1945; Paul McGrath took over as host until the show left the air in 1952. Producer Hiram Brown would utilize the creaking door again in the 1970s, when he produced and directed The CBS Radio Mystery Theater.

Episodes include